JP4820756B2 - Reaction vessel, reaction vessel liquid introduction device, liquid introduction reaction measuring device, and liquid introduction device - Google Patents

Description

【Technical field】
[0001]
The present invention relates to a reaction vessel, a reaction vessel liquid introduction device, a liquid introduction reaction measurement device, and a liquid introduction device.
[Background]
[0002]
In recent years, a polymerase chain reaction (PCR) method has been used in all biological fields as a DNA amplification method for rapidly and easily amplifying a specific DNA fragment. The PCR method is a method in which two primers complementary to a template DNA are designed, and a region sandwiched between the primers is replicated in vitro (in vitro). In this method, PCR products are obtained by amplifying DNA exponentially by repeating temperature cycles of incubating a reaction solution containing template DNA, primers, nucleotides, and heat-resistant DNA polymerase at various temperatures.
[0003]
In one cycle, for a container containing template DNA, primer, DNA polymerase, nucleotide and reaction buffer solution, double-stranded DNA is denatured into single-stranded DNA, and the primer anneals to single-stranded DNA. It consists of incubating under the respective temperature conditions for synthesizing a DNA strand complementary to a single strand, and one molecule of DNA fragment is made into two molecules. In the next cycle, the DNA fragment synthesized in the previous cycle also serves as a template, so that the DNA fragment synthesized after n cycles is 2 ⁿ Become a molecule.
[0004]
Conventionally, the temperature is controlled by accommodating a container made of glass containing template DNA, primers, DNA polymerase, nucleotides, and reaction buffer solution in a housing part of a block thermostat made of a material such as aluminum. Then, the metal block-shaped housing portion is heated or cooled, and the next temperature is heated or cooled by waiting until the liquid temperature has a uniform temperature distribution (Patent Document 1). .
[0005]
For this reason, it takes time until the reaction liquid in the container is heated or cooled, because the capacity of the container is large, so that the temperature distribution of the liquid temperature is uniform. A complicated temperature change occurs due to the difference in specific heat, and there is a problem that it is necessary to give a complicated temperature instruction in order to amplify DNA with high accuracy.
[0006]
By the way, temperature control is important in the PCR method, and the quality and quantity of the PCR product finally obtained can be changed by changing the temperature cycle.
[0007]
In particular, in real-time PCR, the production process of amplification products in PCR is detected and analyzed in real time, whereby more accurate quantification is performed, and more accurate and quick temperature control is required. Therefore, various devices have been proposed (Patent Documents 2 to 5). However, these apparatuses are large-scale and complicated apparatuses in which a complicated flow path is provided, a large-scale centrifugal apparatus or the like is used.
[0008]
On the other hand, the present inventor provided a reaction vessel main body having a reaction chamber for containing the reaction liquid and a lid member capable of sealing the opening of the reaction chamber, and the lid member presses the reaction liquid. The reaction container which has a part was disclosed, and it became possible to perform rapid temperature control with a simple apparatus scale, without requiring a centrifugal force (patent document 6).
[0009]
However, the present inventor uses a large-scale apparatus by combining a thin layer or a thinning of a highly heat-efficient liquid with a rational centrifugal process or a suction discharge process based on the special shape of the container. Therefore, it came to the mind that consistent processing shortening and automation for PCR and the like can be performed simultaneously.
[0010]
[Patent Document 1]
Japanese Patent No. 2622327
[Patent Document 2]
Special Table 2000-511435
[Patent Document 3]
Special table 2003-500674 gazette
[Patent Document 4]
Special table 2003-502656 gazette
[Patent Document 5]
US Patent 5,958,349
[Patent Document 6]
JP 2002-10777 A
DISCLOSURE OF THE INVENTION
[Problems to be solved by the invention]
[0011]
Accordingly, the present invention has been made to solve the above problems, and a first object of the invention is to control the temperature of the liquid contained in the container with high accuracy and faithful response. A reaction vessel, a reaction vessel liquid introduction device, a liquid introduction reaction measuring device, and a liquid introduction device.
[0012]
The second purpose is to shorten the time until the temperature of the liquid is evenly distributed after giving an instruction for heating or cooling, a reaction vessel capable of performing processing quickly, a reaction vessel liquid introduction device, a liquid introduction It is to provide a reaction measuring device and a liquid introducing device.
[0013]
The third object is to obtain a homogeneous reaction and highly accurate optical information by thinning or thinning the liquid with bubbles and gas regions removed from the liquid, and reaction container liquid. It is to provide an introduction apparatus, a liquid introduction reaction measuring apparatus, and a liquid introduction apparatus.
[0014]
The fourth object is a reaction vessel, a reaction vessel liquid introduction device, a liquid introduction reaction measurement device, and a liquid introduction capable of automatically and efficiently performing a consistent process on a liquid to be treated with a simple structure. Is to provide a device.
[Means for Solving the Problems]
[0015]
The first invention communicates between a storage chamber having an opening and capable of storing liquid, a reaction chamber formed thinner or thinner than the storage chamber, and the storage chamber or the outside and the reaction chamber. A container having at least one flow path, the container being formed to be connectable to a liquid introducing portion provided outside, and capable of introducing a liquid into the reaction chamber by connecting to the liquid introducing portion It is.
[0016]
Here, the “reservoir chamber” is a portion capable of storing a liquid, and is provided to facilitate introduction of the liquid into the reaction chamber. The introduction of the liquid into the storage chamber is performed from the opening or through the flow path.
[0017]
The size or thickness of the storage chamber is such that liquid can be easily introduced into the storage chamber from the opening basically by gravity, or a rotating body can be connected to the opening. Size or thickness.
[0018]
In the “reaction chamber”, liquid can be easily introduced by gravity alone without gas contamination. Absent Thinness (thinness). The thickness or thickness of the reaction chamber is, for example, 0.1 mm to 3 mm. Along with this, the amount of liquid handled corresponds to, for example, several μl to 300 μl. Depending on this amount, the processing time of the PCR method corresponds to about several minutes to several tens of minutes. For example, as the shape of the reaction chamber, the size of the maximum side surface is, for example, a square with a length of 5 mm or 3 mm or a circle with a radius of 5 mm or 3 mm and a thickness of about 1 mm. The volume is 25 μl or 9 μl.
[0019]
The “flow channel” is a portion that communicates between the storage chamber or the outside and the reaction chamber, and is a portion through which liquid is exclusively passed. For example, the “flow channel” is formed thinner or thinner than the storage chamber. For example, a portion that is formed with a narrow width between the thinned reaction chamber or a portion having a thickness different from that of the reaction chamber, for example, between the thinned reaction chamber and the thinned reaction chamber. It is. By communicating with the flow path, the liquid can be reliably introduced, the container can be made compact or the reaction chamber can be easily sealed, and the reaction chamber can be separated from the storage chamber with respect to the rotation axis. It is easy to be located far away. In order to introduce the liquid in a state in which the gas mixture is excluded from the reaction chamber, for example, a centrifugal force or a suction force is used.
[0020]
The reason for providing a “reaction chamber” is that by introducing the liquid into the reaction chamber, at least the heat conduction time in the thickness direction of the liquid is shortened, and heat or temperature is transmitted to the liquid in a short time, and the liquid is quickly This is to improve the efficiency of the heat treatment so that a temperature distribution that makes the temperature uniform can be achieved. Therefore, heating or cooling can be performed by bringing the reaction chamber into contact with or approaching a solid or liquid heating / cooling medium, or by blowing hot or cold air with a dryer. Furthermore, the reaction chamber is heated by the heating / cooling medium, for example, on the wall surface having the largest area among the wall surfaces surrounding the reaction chamber, or sandwiched from both sides along the normal direction of the wall surface having the largest area, or Cooling. In order to obtain optical information by fluorescence when a target substance or the like is labeled with a fluorescent substance, for example, the large wall surface is irradiated with excitation light and received from the same large or small wall surface.
[0021]
The “container” has a portion (here, a storage chamber) capable of storing liquid, and has such a liquid suction / discharge port in addition to one opening. Such a dispensing tip shape may be used. Since the container has an opening in the storage chamber, in order to perform the function as a container, the opening is not limited even when the liquid introduction part is a rotating body and the container is connected to the rotating body. It is necessary to connect so that the liquid does not go out. That is, the opening is not connected downward and sideways without being blocked by the rotating body or other lid. Therefore, when the opening is not closed with a cap or the like, the opening needs to be opened upward so that liquid can be stored when used as a container or when connected to a rotating body. At the time of connection to the rotating body, the opening direction of the opening and the rotation axis of the rotating body are along the vertical direction. The opening may be provided with a cap that closes the opening.
[0022]
The container has a reaction chamber that has only one opening or communicates with only one flow path, and is called a fluid storage section, and has two or more openings or communicates with two or more flow paths. A case having a reaction chamber is called a fluid circuit. The dispensing tip-shaped container or some containers shown in the embodiments described later correspond to a fluid circuit. In the case of a fluid circuit, the liquid is introduced by introducing liquid from a part of the openings or channels provided in the reaction chamber and discharging gas from the other openings or channels. Can be performed efficiently and smoothly. Further, since it is possible to more reliably prevent gas and bubbles from being mixed into the liquid introduced into the storage chamber, uniform and highly accurate temperature control and accurate optical information for the liquid in the reaction chamber can be measured. It becomes possible. The partial opening or flow path of the reaction chamber is always in communication with the storage chamber.
[0023]
“Liquid introduction part” introduces liquid from the storage chamber to the reaction chamber or from the outside to the reaction chamber, or moves liquid from the storage chamber through the reaction chamber to the outside or from the outside through the reaction chamber to the storage chamber. In this case, the portion has a function of introducing a liquid into the reaction chamber, and is provided so as to be connectable to the container. For introducing the liquid, for example, a nozzle provided with a rotation mechanism for a container that is introduced into the reaction chamber by applying centrifugal force to the liquid and a suction / discharge mechanism that is introduced into the reaction chamber by sucking the liquid is used.
[0024]
For “connection”, the reaction vessel is attached to the liquid introduction part, fitted, fitted, inserted, fitted, fitted, coupled, screwed, intimately, or closely adhered, or the reaction The whole container is accommodated or attached to the liquid introduction part, or other attachment, contact, or accommodation methods similar to these in consideration of the gist of the invention are included. The rotating body may be connected on the upper side of the reaction vessel or connected on the lower side of the reaction vessel. Since “having one flow path”, the reaction chamber needs to have at least one opening for introducing or exhausting liquid or gas.
[0025]
According to the reaction container of the first invention, the liquid can be easily thinned or thinned by introducing the liquid from the storage chamber into the reaction chamber. By using this reaction vessel, the temperature of the liquid can be controlled with high accuracy and faithful response.
[0026]
By thinning or thinning the liquid with the reaction vessel or the reaction vessel liquid introduction device, the time until the liquid temperature becomes an even temperature distribution after giving an instruction to heat or cool the liquid is shortened. Thus, processing can be performed quickly and efficiently.
[0027]
According to the reaction vessel or the reaction vessel liquid introduction device, by using centrifugal force or the like, the reaction vessel or the reaction vessel liquid introduction device can be thinned or thinned in a state where bubbles and gas are removed from the liquid. Therefore, in temperature control, a uniform temperature distribution can be obtained, and highly accurate optical information can be measured.
[0028]
Moreover, according to this reaction container, it is trying to communicate between the storage chamber or the exterior, and the reaction chamber by providing one flow path. As a result, the reaction chamber and the storage chamber can be separated from each other in distance. Therefore, a large centrifugal force can be applied to the liquid to be introduced for the reaction vessel liquid introducing device based on the centrifugal force. In addition, for the reaction container liquid introduction device based on the suction and discharge force, the tip of the flow path can be inserted into various containers by communicating between the outside and the reaction chamber via a thin flow path. . In addition, even a small amount of liquid can be easily sucked and handled. Further, the reaction chamber can be easily sealed by closing the flow path.
[0029]
In addition, according to the reaction container, it is possible to facilitate introduction of the liquid into the reaction chamber by providing the reaction container with a storage chamber and allowing the liquid to be temporarily stored in the storage chamber.
Furthermore, by providing the reaction vessel detachably with respect to a liquid introduction part such as a rotating body provided outside, the reaction vessel can be formed in a disposable manner, so that processing can be performed at low cost.
[0030]
The second invention is a reaction vessel in which at least a part of the reaction chamber has translucency or translucency.
Here, “partially translucent or semi-translucent reaction chamber” is used for obtaining optical information in the reaction chamber, such as DNA labeled with fluorescence by real-time PCR. This is to measure the amount and concentration of genetic material.
[0031]
Here, “real-time PCR” refers to a method of performing PCR while measuring the amount of amplified DNA in real time. Real-time PCR has the advantage that no electrophoresis is required, amplification can be observed during the temperature cycle, and quantitative results can be obtained. As a method usually performed using a fluorescent reagent, a cycling probe method, an intercalator method, a TaqMan probe method, Molecular Beacon method There is.
[0032]
According to the second invention, since at least a part of the reaction chamber has translucency or semi-translucency, optical information in the reaction chamber can be easily obtained in real-time PCR or the like. When the reaction chamber is not light-transmitting or semi-light-transmitting, optical information can be obtained by providing an optical waveguide in the reaction chamber.
[0033]
3rd invention is a reaction container in which the said opening part has a cap which can be connected to this opening part so that attachment or detachment is possible.
[0034]
Here, the cap is capable of sealing the opening, and the opening and the cap are, for example, mounted, fitted, screwed, fitted, fitted, fitted, connected, They are connected by means of close contact, close contact, etc., and contact methods. Further, the cap may be provided, for example, so that it can be attached to the lower end portion of the rotating body of the liquid introducing portion by mounting or the like. Thereby, leakage of liquid or gas from the opening can be prevented.
[0035]
According to the third invention, by providing a cap that can be detachably connected to the opening, it is possible to prevent the liquid stored in the storage chamber from leaking from the opening to the outside. Furthermore, when the liquid introduction part can be detachably connected to the cap, contact between the liquid and the liquid introduction part can also be prevented.
[0036]
In particular, when the liquid introduction part is the rotating body, a cap that covers the lower end of the rotating body is detachably provided so that the opening of the container is connected through the cap. When the rotator is rotated at a high speed, the liquid scatters and the rotator directly contacts the liquid in the container, so that cross contamination can be surely avoided. Further, by preventing the liquid from scattering upward, the liquid can be introduced into the reaction chamber more efficiently than when the liquid is pushed back downward.
[0037]
The fourth invention is a reaction vessel in which the flow path and the reaction chamber are formed of a flat frame having grooves or holes and a soft material film covering the frame from one side or both sides. .
Here, the “film” includes a thin plate.
[0038]
According to the fourth invention, by forming a flat frame having grooves or holes with a soft material film covering from one side or both sides, even if the reaction vessel has a complicated structure, it can be easily and inexpensively. A reaction vessel having a sealable reaction chamber can be produced.
[0039]
In a fifth aspect of the present invention, the flow path communicates between the reaction chamber and the storage chamber, the liquid introduction section is a rotatable rotating body, and the reaction vessel is rotated. The rotation axis of the rotating body penetrates the container, and the reaction chamber is positioned farther from the rotation axis than the storage chamber and is connected to the rotating body. It is a reaction vessel which can be rotated together.
[0040]
“When the reaction vessel is connected to the rotating body, the rotation axis of the rotating body penetrates the container and the reaction chamber is formed farther from the rotation axis than the storage chamber” Therefore, the container can be rotated by the rotating body. The “rotation axis” is different from a specific rotation axis and means an abstract rotation center line.
[0041]
Note that “the object rotates” means that the object rotates around a rotation axis that penetrates the object, and a concept for the revolution in which the object rotates around the rotation axis provided outside the object. It is. The liquid stored in the storage chamber is moved by centrifugal force to the reaction chamber connected to a position farther from the rotation axis than the storage chamber by the high-speed rotation of the rotating body, and the gas has a specific gravity higher than that of the liquid. Since it is small, the liquid moves closer to the axial center than the liquid, and the liquid can be introduced in a state where no gas is mixed into the reaction chamber. Furthermore, if the reaction chamber is placed below the storage chamber, gravity can also be used, so that the introduction of liquid into the reaction chamber is further facilitated. Here, “high speed rotation” is, for example, several hundred rpm to several thousand rpm.
[0042]
Further, since “the reaction chamber is located farther from the rotational axis than the storage chamber”, for example, as shown in FIG. 1, a storage chamber having an opening, and a communication between the storage chamber and the storage chamber A reaction chamber that is thinner than the chamber and formed in a layered manner, or a tubular or thin-layered reaction chamber that extends obliquely downward from the lower side of the thick tubular storage chamber having an opening on the upper side. There are cases. With regard to “distant”, for example, it is determined that the longer the distance between the center of gravity or the center of the target portion and the rotation axis, the longer.
[0043]
Since “the container can be connected to the rotating body”, the container has a portion that can be connected to the rotating body, that is, a connecting portion. The connecting portion may be, for example, the opening, a part of another container, or the entire container. Since such a connecting portion itself is a part of the container or the entire container, the rotation axis passes through the container. “Connecting” includes mounting, fitting, screwing, fitting, fitting, fitting, or accommodation of the entire container, or other attachment methods for a portion of the container or the entire container. The rotating body may be connected on the upper side of the reaction vessel or connected on the lower side of the reaction vessel. In addition, you may make it perform the connection of the said reaction container to a liquid introducing | transducing part through the said cap.
[0044]
Here, when connecting an opening part and a rotary body by fitting or screwing, the shape of the connection part of the opening part and a rotary body needs to correspond. For example, for a cylinder it is necessary to have a cylindrical inner surface. Moreover, when connecting an opening part and a rotary body by screwing, the rotation direction by the said rotary body is a direction which the said rotary body advances by screwing with respect to an opening part. In this case, the axis of the opening coincides with the rotation axis.
[0045]
Further, for example, by providing a rotation support shaft that protrudes below the container along the rotation axis, it is possible to apply a stable rotation that does not shake the rotation shaft.
[0046]
In the present invention, since the reaction vessel can rotate, it is not necessary to apply centrifugal force with a large centrifugal device, and the scale of the device can be reduced. In addition, if a rotatable nozzle, which will be described later, is used, the processing using the container can be consistently automated.
[0047]
According to a fifth aspect of the present invention, the flow path is provided so as to communicate between the reaction chamber and the storage chamber, a rotatable rotating body is provided as a liquid introducing portion, and the rotation axis of the rotating body is The reaction chamber is formed so as to be located farther from the rotation axis than the storage chamber through the container. That is, the reaction vessel rotates by rotation by a rotating body to which the reaction vessel is connected, and by this rotation, centrifugal force is applied to the liquid, and the liquid or liquid is suspended in a state where gas and bubbles are removed by centrifugation. Solids can be reliably introduced into the reaction chamber. Further, since the liquid is introduced by the rotation of the reaction vessel, the introduction can be performed reliably without taking up space.
[0048]
That is, since the liquid can be introduced into the reaction chamber by the rotation of the container, a large space that revolves around the rotation axis provided outside the reaction container is not required, and basically one container size. The liquid can be introduced using a small rotating device.
[0049]
In addition, when connected to the opening so that the rotation axis of the rotating body passes through the opening of the storage chamber, the opening used for introducing the liquid is also used for connecting the rotating body. Therefore, it is not necessary to newly provide a mounting portion for the rotating body in the container, and the structure is simplified.
[0050]
In addition, the rotating body and the reaction vessel can be reliably and easily connected by screwing or fitting. Especially when the rotating body is attached by screwing, the rotation of the rotating body can be used. So it is efficient.
[0051]
In a sixth aspect of the invention, the rotating body is a rotatable nozzle capable of sucking and discharging gas, and the nozzle is a reaction vessel having a rotation axis along the axial direction thereof.
[0052]
The “nozzle” is preferably formed so that not only the container but also a dispensing tip can be connected. Since the liquid can be dispensed and transferred through the dispensing tip, it is possible to perform a more diverse process. The nozzle is preferably provided in a dispensing device having suction / discharge means for sucking and discharging a liquid therethrough, and can be moved up and down and horizontally by a technique apparent to those skilled in the art. Thereby, the liquid accommodated in the container provided outside can be transferred to another container.
[0053]
According to the sixth invention, a nozzle capable of rotating is used as the rotating body. Therefore, in addition to thinning or thinning the liquid by introducing the liquid into the reaction chamber, it can be used for dispensing the liquid into the reaction vessel and can be applied to various processes. Processing can be consistently automated. Further, since the rotation axis coincides with the axis of the nozzle, the rotation radius is small, and the apparatus scale can be suppressed.
[0054]
In a seventh aspect of the invention, the flow path includes a liquid introduction flow path for introducing a liquid from the storage chamber to the reaction chamber, and an exhaust flow path for exhausting gas from the reaction chamber. The liquid introduction part has a rotatable rotating body, and the reaction vessel is connectable to the rotating body, and when connected, the reaction chamber is farther from the rotation axis than the storage chamber. It is the reaction container which is formed so that it may be located and can rotate with this rotary body.
[0055]
Here, since two flow paths are provided in the reaction chamber, the reaction chamber has two openings for introducing or exhausting liquid or gas. Here, the reason for providing the two flow paths, the liquid introduction flow path and the exhaust flow path, is to remove the gas reliably and efficiently in order to introduce the liquid in a state where it does not mix with the gas in the reaction chamber. Because. The gas to be exhausted through the exhaust passage may be returned to the storage chamber or discharged to the outside. As a result, liquid introduction and gas removal can be performed quickly and smoothly.
[0056]
Further, the rotation axis of the rotating body may penetrate the container or may not penetrate the container. When it penetrates the container, it rotates, but when it does not penetrate, the reaction container revolves around the rotation axis.
[0057]
By forming the liquid introduction flow path so as to be located farther from the rotation axis when the rotating body is connected than the exhaust flow path, the exhaust flow path is configured to be a liquid introduction flow. Since the influence of the centrifugal force is smaller than that of the road, the exhaust can be performed smoothly. In this case, if at least a part of the exhaust passage is provided along the rotation axis when the rotating body is connected, the influence of the centrifugal force on the exhaust passage can be further reduced. it can. Since “connection” has already been described, the description thereof is omitted.
The reaction chamber is formed in, for example, a substantially cylindrical shape, and the side surface of the reaction chamber is smaller in area than both bottom surfaces and thinner than the storage chamber.
[0058]
According to the seventh aspect of the invention, a liquid introduction flow path for introducing a liquid from the storage chamber to the reaction chamber and an exhaust flow path for exhausting gas from the reaction chamber are provided, and the liquid introduction section By using the rotating body, the introduction of the liquid and the exhaust of the gas are performed using separate flow paths, so that the introduction of the liquid and the exhaust of the gas can be performed efficiently and quickly.
[0059]
The eighth invention is a reaction vessel in which a deformable soft member is provided in at least a part of the flow channel or the reaction chamber, and the reaction chamber can be sealed by deforming the soft member.
[0060]
Here, the “soft member” is a member formed of a soft material that can be deformed by applying pressing force, ultrasonic waves, high frequency, vibration, laser, heat, or the like. The soft member is a member formed of, for example, an elastic body such as rubber, plastic including polyethylene or silicone, and the like. The soft member includes, for example, a film-shaped member surrounding the flow path or the reaction chamber, or a block-shaped member described later provided in the flow path or the reaction chamber.
[0061]
In order to deform the soft member, for example, by pressing a reaction chamber formed by a soft material or a wall of a flow path, or by applying ultrasonic waves, high frequency, laser, heat, etc., the soft member is welded. To do. When the soft member is formed of an elastic body such as rubber and is deformed by a pressing force, it is necessary to maintain the pressure on the elastic body from the outside in order to keep the deformation.
[0062]
According to the eighth invention, a deformable soft member is provided in at least a part of the flow path or the reaction chamber, the reaction chamber can be sealed by deforming the soft member, and gas is mixed therein. It is easy to obtain a thinned or capillaryed liquid. Accordingly, the introduced liquid is prevented from flowing out of the reaction chamber, so that the liquid can be introduced efficiently and quickly.
[0063]
According to a ninth aspect of the invention, the soft member is an elastic block member that can be deformed by pressing, and a reaction vessel having a gap through which liquid and gas can pass.
Here, the “void” includes a through hole. An example of the “elastic block member” having a gap inside is an elastic valve body described later. In order to seal the reaction chamber, it is necessary to continuously apply pressure to the elastic block member.
[0064]
According to the ninth aspect of the present invention, the elastic block member having a gap through which liquid or the like can pass is provided in the flow path or the reaction chamber, and the liquid is reliably and easily supplied to the reaction chamber by pressing. Can be sealed. Further, this prevents the introduced liquid from flowing out of the reaction chamber, so that the liquid can be introduced efficiently and quickly.
[0065]
A tenth aspect of the invention is a reaction container having a rotation support shaft along the rotation axis of the rotating body when the reaction container is connected to the rotating body.
[0066]
The “rotation support shaft” is a shaft provided so that the reaction vessel can be smoothly rotated with the rotation of the rotating body. For example, when the reaction vessel is connected to a rotating body at the opening of the storage chamber, the rotation support shaft is provided so as to protrude downward from the reaction vessel, or the rotation support protruding downward. The shaft may also be protruded from information so that the upper end of the rotation support shaft is connected to the rotating body. Since the rotation support shaft is also a part of the reaction vessel, in this case, the rotation axis of the rotating body penetrates the vessel and corresponds to rotation.
[0067]
According to the tenth invention, when the reaction vessel is connected to the rotating body, and the rotation axis of the rotating body passes through the container, the rotation support shaft that protrudes below the container along the rotation axis. Is attached to a bearing provided outside and the rotating body is rotated, whereby the reaction vessel can be rotated in a stable state with respect to the rotation axis.
[0068]
In an eleventh aspect of the invention, the opening is detachably connected by a lower end of the rotating body or a cap that is detachably connectable to the lower end of the rotating body in a state of being penetrated by the rotation axis of the rotating body. A reaction vessel that is possible.
[0069]
According to the eleventh aspect of the present invention, a cap is provided at the lower end of the rotating body, and the opening of the container is connected through the cap. It is possible to prevent the rotator from coming into direct contact with the liquid in the container by scattering and to reliably avoid cross contamination. Further, by preventing the liquid from scattering upward, the liquid can be introduced into the reaction chamber more efficiently than when the liquid is pushed back downward.
[0070]
In a twelfth aspect of the invention, the rotating body is a nozzle capable of sucking and discharging gas, and the nozzle is a reaction vessel having an axial direction or a rotation axis parallel to the axial direction.
[0071]
According to the twelfth aspect, by using the nozzle as the rotating body, it can be used as a dispensing device, and various processes can be automated consistently.
[0072]
In a thirteenth aspect of the present invention, the storage chamber and the reaction chamber communicate with each other, and the flow chamber communicates with the reaction chamber and the outside. The liquid introducing unit sucks gas through the nozzle and the nozzle. It has a suction / discharge section that discharges, and the opening of the storage chamber is a reaction container that can be connected by the nozzle.
[0073]
Here, “connection” includes a contact or attachment method such as mounting, fitting, screwing, fitting, fitting, fitting, welding, or close contact.
[0074]
Further, the reaction chamber communicates with the storage chamber at the upper part, for example, and the suction / discharge port is provided at the lower end of the flow path communicating with the lower part of the reaction chamber, for example. Here, by forming the channel with a small diameter, it is possible to cope with various containers provided outside. The size of the storage chamber is a size that allows the fluid to be introduced into the reaction chamber by the suction of the fluid, or a size that enables suction and discharge by the nozzle. Accordingly, the fluid is introduced into the reaction chamber from the suction / discharge port by the suction of the fluid by the nozzle.
[0075]
In addition, it is preferable that this nozzle is provided in the dispensing apparatus which can be moved horizontally and vertically. This makes it possible to perform further various processes by moving the nozzles to containers provided at various positions. The nozzle does not necessarily allow rotational movement including rotation, but if rotational movement is possible, it will also help to homogenize the liquid.
[0076]
The storage chamber and the reaction chamber may communicate with each other through a flow path, or may directly communicate with each other between the storage chamber and the reaction chamber. In the thirteenth invention, since it has two flow paths, the reaction chamber has two openings between the flow paths.
[0077]
According to the thirteenth invention, the liquid is introduced into the reaction chamber by using the nozzle as a liquid introduction portion and sucking the liquid through the reaction chamber to the storage chamber by the suction and discharge portion. ing. Therefore, the liquid can be reliably introduced into the reaction chamber without mixing gas or bubbles. In this case, since it is not necessary to rotate the nozzle, the mechanism for introducing the liquid into the reaction chamber is simplified.
[0078]
In a fourteenth aspect of the invention, the reaction chamber is accommodated in a pipette tip composed of a large diameter portion and a narrow diameter portion thinner than the large diameter portion with a spacer interposed between the inner surface of the pipette tip. A gap formed between the outer surface of the core and the inner surface of the pipette tip, and the storage chamber is a space in the large-diameter portion formed above the reaction chamber, and the small-diameter portion of the pipette tip Is a flow path that communicates the outside with the reaction chamber, and the opening of the large-diameter portion is a reaction vessel that can be connected by the nozzle.
[0079]
Examples of the spacer include a plurality of protrusions protruding outward from the outer surface of the core, or protrusions protruding inward from the inner surface of the pipette tip. This gap needs to communicate with the upper part of the small diameter part and the large diameter part.
[0080]
In this case, the nozzle which is the liquid introducing portion may be rotatable, and the nozzle may have a rotation axis along the axial direction thereof. In this case, the rotation of the nozzle facilitates the introduction of the liquid into the reaction chamber and can also homogenize the liquid.
[0081]
According to the fourteenth aspect of the present invention, the core is accommodated in the pipette tip, the gap formed between the outer surface of the core and the inner surface of the pipette tip is used as the reaction chamber, and the space in the large-diameter portion above the reaction chamber is used. A storage chamber is used, and a nozzle can be connected to the storage chamber, that is, the opening of the large diameter portion. Therefore, the liquid can be introduced into the reaction chamber by sucking the liquid stored in the container provided outside from the small diameter portion by the nozzle from the reaction chamber toward the storage chamber. Further, the product produced by the reaction in the reaction chamber is discharged from the nozzle to discharge the product into the container through the small diameter portion from the reaction chamber to easily obtain the product. Can do.
[0082]
A fifteenth aspect of the invention is a reaction vessel in which various predetermined biological materials are arranged at predetermined positions on the outer surface of the core.
[0083]
Thereby, for example, a target substance labeled with a luminescent substance such as a fluorescent substance and various predetermined biological substances are arranged at predetermined positions, and a liquid in which the target substance is suspended is introduced into the reaction chamber. Thus, it is possible to analyze the structure of the target substance or analyze its properties by measuring the light emission position.
[0084]
In order to arrange a predetermined biological material at a predetermined position on the outer surface of the core, in addition to directly fixing the predetermined biological material at a predetermined position on the outer surface of the core, a string shape, a thread shape, etc. In some cases, a predetermined biological material fixed at a predetermined position on the elongated medium is wound around the outer surface of the core. In this case, the biological material can be easily accumulated and arranged by arranging the biological material on the medium and winding the arranged medium around the core. Alternatively, the light emission position and the like can be easily detected by following the medium.
[0085]
According to the fifteenth aspect, by fixing various predetermined biological substances to predetermined positions on the outer surface of the core, the light emission position of the labeled target substance that has reacted with the biological substances is measured. Thus, the target substance can be analyzed.
[0086]
A sixteenth aspect of the invention is a reaction vessel in which the reaction chamber can be sealed by closing between the nozzle or the storage chamber and the reaction chamber and between the reaction chamber and the outside.
[0087]
In order to close the gap between the nozzle and the reaction chamber, for example, a first cap is detachably fitted on the upper portion of the large-diameter storage chamber, and the cap itself is detachably attached to the nozzle. Provide freely connectable. The cap connected to the upper portion of the large-diameter portion can be further moved downward in the upper portion of the pipette tip, and the cap is moved downward to come into contact with the upper end of the core stored in the pipette tip. To close the reaction chamber from above. Moreover, about the lower side of a reaction chamber, the reaction chamber is obstruct | occluded from the upper and lower sides by inserting and connecting the front-end | tip of the said small diameter part to a 2nd cap.
[0088]
On the other hand, in order to close the space between the storage chamber and the reaction chamber and between the reaction chamber and the outside, a part or all of the flow path or the reaction chamber is formed of a deformable soft material, and the reaction chamber Is performed by deforming the soft material. These caps, moving means, or pressing means for performing deformation correspond to sealing means.
[0089]
According to the sixteenth aspect, by efficiently and quickly introducing the liquid by sealing the reaction chamber and quickly and easily preventing the liquid introduced into the reaction chamber from flowing out of the reaction chamber. Can do.
[0090]
In a seventeenth aspect of the invention, the reaction chamber is formed in a substantially cylindrical shape, and the side surface of the reaction chamber is smaller in area than both bottom surfaces and the height between both bottom surfaces is thinner than the thickness of the storage chamber. Reaction vessel.
[0091]
According to the seventeenth aspect, by forming the reaction chamber in a substantially cylindrical shape, uniform light information can be obtained by irradiating or receiving light on the side surface.
[0092]
In an eighteenth aspect of the invention, there are one or more reaction vessels and one or more liquid introduction portions to which the reaction vessels can be detachably connected. The reaction vessel has an opening and stores the liquid. A possible storage chamber, a reaction chamber formed thinner or thinner than the storage chamber, and at least one flow path communicating between the storage chamber or the outside and the reaction chamber, It is a reaction vessel liquid introduction device introduced into the reaction chamber.
[0093]
Here, the “liquid introducing unit” refers to, for example, a rotatable rotating body that can be connected to the reaction vessel and a rotation driving unit that drives the rotating body, or a nozzle that is connected to the reaction vessel and the nozzle. It is a suction / discharge section that sucks or discharges gas. The rotating body may be a nozzle at the same time. Moreover, it is preferable that the liquid introduction part is movable relative to an external container or the like that contains or can accommodate a reagent or the like. Thereby, the automation of the process can be further advanced.
[0094]
In order to make “removably connectable”, for example, a reaction vessel is arranged in advance, the connecting portion of the liquid introduction part is moved and connected by fitting, screwing, etc. This is performed by moving a plate for scraping the reaction vessel from the connection portion or by rotating in a direction opposite to the screwing direction.
[0095]
By introducing the liquid into the reaction chamber from the reaction container liquid introduction device storage chamber according to the eighteenth aspect of the invention, the liquid can be easily made thin or thin. By using this reaction vessel, the temperature of the liquid can be controlled with high accuracy and faithful response.
[0096]
By thinning or thinning the liquid with the reaction vessel or the reaction vessel liquid introduction device, the time until the liquid temperature becomes an even temperature distribution after giving an instruction to heat or cool the liquid is shortened. Thus, processing can be performed quickly and efficiently.
[0097]
According to the reaction vessel or the reaction vessel liquid introduction device, by using centrifugal force or the like, the reaction vessel or the reaction vessel liquid introduction device can be thinned or thinned in a state where bubbles and gas are removed from the liquid. Therefore, in temperature control, a uniform temperature distribution can be obtained, and highly accurate optical information can be measured.
[0098]
Moreover, according to this reaction container, it is trying to communicate between the storage chamber or the exterior, and the reaction chamber by providing one flow path. As a result, the reaction chamber and the storage chamber can be separated from each other in distance. Therefore, a large centrifugal force can be applied to the liquid to be introduced for the reaction vessel liquid introducing device based on the centrifugal force. In addition, for the reaction container liquid introduction device based on the suction and discharge force, the tip of the flow path can be inserted into various containers by communicating between the outside and the reaction chamber via a thin flow path. . In addition, even a small amount of liquid can be easily sucked and handled. Further, the reaction chamber can be easily sealed by closing the flow path.
[0099]
In addition, according to the reaction container, it is possible to facilitate introduction of the liquid into the reaction chamber by providing the reaction container with a storage chamber and allowing the liquid to be temporarily stored in the storage chamber.
Furthermore, by providing the reaction vessel detachably with respect to a liquid introduction part such as a rotating body provided outside, the reaction vessel can be formed in a disposable manner, so that processing can be performed at low cost.
[0100]
In a nineteenth aspect of the invention, the liquid introduction unit includes a rotatable rotating body and a rotation driving unit that rotationally drives the rotating body, and the reaction chamber of the reaction vessel connected to the rotating body includes the The reaction vessel is formed so as to be located farther from the rotation axis of the rotating body than the storage chamber, and the reaction container rotates by the rotation of the rotating body to introduce the liquid stored in the storage chamber into the reaction chamber. This is a reaction vessel liquid introducing device.
[0101]
According to this apparatus, a centrifugal force is applied to the liquid in the storage chamber of the reaction vessel, and the liquid is introduced into the reaction chamber located farther from the rotation axis than the storage chamber without gas being mixed therein. Can do. As the reaction vessel, the reaction vessel according to the first to fifteenth inventions can be used.
[0102]
Here, the rotation axis may rotate through the container or revolve through the outside of the container. In the case of rotation, the scale of the apparatus can be reduced, and various processes can be performed with a compact apparatus by using the nozzle itself as a rotating body. In the case of revolution, a strong centrifugal force can be applied.
[0103]
The “connection” is as described in the fifth invention.
Here, in order to rotate, the rotation axis of the rotating body connected to the container needs to be formed so as to penetrate the container. In addition, it is preferable that the rotation axis of the rotating body can be connected to the opening so as to penetrate the opening of the storage chamber.
[0104]
Thereby, since the opening is covered with the rotating body, it is possible to prevent liquid leakage from the opening without covering the opening with a cap or the like.
According to the nineteenth invention, a rotatable rotating body is provided as the liquid introducing portion, and the reaction chamber is formed farther from the rotation axis than the storage chamber. That is, the reaction vessel rotates or revolves by rotation by a rotating body to which the reaction vessel is connected, and by this rotation or revolution, a centrifugal force is applied to the liquid, and the liquid or liquid is removed in a state where gas or bubbles are removed by centrifugation. It is possible to reliably introduce the solid suspended in the reaction chamber. In addition, when the liquid is introduced by the rotation of the reaction vessel, the introduction can be performed reliably without taking up space. That is, since the liquid can be introduced into the reaction chamber by the rotation of the container, a large space that revolves around the rotation axis provided outside the reaction container is not required, and basically one container size. The liquid can be introduced using a small rotating device. On the other hand, when performing revolution, a large centrifugal force can be obtained at a low rotational speed.
[0105]
In addition, when connected to the opening so that the rotation axis of the rotating body passes through the opening of the storage chamber, the opening used for introducing the liquid is also used for connecting the rotating body. Therefore, it is not necessary to newly provide a mounting portion for the rotating body in the container, and the structure is simplified.
[0106]
In addition, the rotating body and the reaction vessel can be reliably and easily connected by screwing or fitting. Especially when the rotating body is attached by screwing, the rotation of the rotating body can be used. So it is efficient.
[0107]
In a twentieth aspect of the invention, the rotating body is a nozzle capable of sucking and discharging a gas, and the rotation axis of the nozzle is along the axial direction of the nozzle or parallel to the axial direction of the nozzle. Device.
[0108]
Since the nozzle also serves as a rotating body, it is possible to connect a dispensing tip and consistently perform various processes such as suction and discharge of liquid and homogenization of suspension. In addition, the rotating body needs to have a moving part that can move in the vertical direction. However, if the rotating body can also move in the horizontal direction, it can be further variously moved by moving the rotating body to containers provided at various positions. It is possible to perform the process.
[0109]
According to the twentieth invention, by using the nozzle as the rotating body, it can be used as a dispensing device, and various processes can be consistently automated.
[0110]
In a twenty-first aspect, the flow path of the reaction vessel includes a liquid introduction flow path for introducing liquid into the reaction chamber from the storage chamber or the outside, and an exhaust for exhausting gas from the reaction chamber. And at least part or all of the flow path or the reaction chamber is formed of a deformable soft member, and a predetermined portion of the soft member is pressed to seal the reaction chamber This is a reaction vessel liquid introduction device having a pressing part.
[0111]
Here, the liquid introduction part is a rotating body in the former combination, and is a nozzle and a suction discharge part in the latter combination. In the latter case, for example, the reaction chamber communicates with the storage chamber in the upper portion, and the liquid introduction flow path is a flow path extending downward from the reaction chamber, and the flow path is formed in a small diameter. By doing so, it can be inserted into various containers provided outside. The exhaust passage communicates between the reaction chamber and a storage chamber provided thereabove, and the nozzle is connected to, for example, an opening on the upper side of the storage chamber. Like that. It communicates upward via the exhaust passage.
[0112]
According to the invention, in the case of the latter combination, liquid is introduced into the reaction chamber through the liquid introduction flow path by suction of fluid by the nozzle, and the gas in the reaction chamber is It will be sucked into the nozzle through the storage chamber via the exhaust passage. At that time, a part of the liquid may be sucked into the storage chamber.
[0113]
According to the twenty-first aspect, a deformable soft member is provided in at least a part of the flow path or the reaction chamber, the reaction chamber can be sealed by deforming the soft member, and gas is mixed therein. It is easy to obtain a thinned or capillaryed liquid. Accordingly, the introduced liquid is prevented from flowing out of the reaction chamber, so that the liquid can be introduced efficiently and quickly.
[0114]
According to a twenty-second aspect of the present invention, in the reaction container, the storage chamber and the reaction chamber communicate with each other and a flow path communicates the reaction chamber with the outside. The liquid introduction unit includes a nozzle and the nozzle. And having a suction / discharge portion for sucking and discharging gas through the opening, and the opening of the storage chamber can be connected to the lower end of the nozzle or the lower end of the nozzle via a cap connectable to the lower end of the nozzle. Reaction vessel liquid introduction device.
[0115]
According to the twenty-second aspect, the liquid is introduced into the reaction chamber by using the nozzle as the liquid introduction portion so that the suction and discharge portion sucks the liquid through the reaction chamber to the storage chamber. ing. Therefore, the liquid can be reliably introduced into the reaction chamber without mixing gas or bubbles. In this case, since it is not necessary to rotate the nozzle, the mechanism for introducing the liquid into the reaction chamber is simplified.
[0116]
In a twenty-third aspect of the invention, the reaction chamber of the reaction vessel includes an outer surface of a core accommodated in a pipette tip having a large diameter portion and a narrow diameter portion thinner than the large diameter portion, and an inner surface of the pipette tip. The storage chamber is a space in the large-diameter portion formed above the reaction chamber, and the small-diameter portion of the pipette tip communicates the outside and the reaction chamber. It is a flow path, and the opening part of the said large diameter part is a reaction container liquid introduction apparatus which can be connected by the said nozzle.
[0117]
According to the twenty-third aspect, the core is accommodated in the pipette tip, the gap formed between the outer surface of the core and the inner surface of the pipette tip is used as the reaction chamber, and the space in the large-diameter portion above the reaction chamber is used. A storage chamber is used, and a nozzle can be connected to the storage chamber, that is, the opening of the large diameter portion. Therefore, the liquid can be introduced into the reaction chamber by sucking the liquid stored in the container provided outside from the small diameter portion by the nozzle from the reaction chamber toward the storage chamber.
Further, the product produced by the reaction in the reaction chamber is discharged from the nozzle to discharge the product into the container through the small diameter portion from the reaction chamber to easily obtain the product. Can do.
[0118]
A twenty-fourth aspect of the invention is a reaction vessel liquid introducing device having sealing means for fluidly closing between the nozzle or the storage chamber and the reaction chamber and between the reaction chamber and the outside.
[0119]
Here, as the “sealing means”, for example, between the nozzle and the reaction chamber, a first cap is detachably and detachably provided on the upper portion of the large-diameter storage chamber, The cap itself is detachably connected to the nozzle. The cap connected to the upper part of the large-diameter part is further moved downward in the upper part of the pipette tip, thereby contacting the upper end of the core accommodated in the pipette tip, thereby closing the reaction chamber from above. To do. Further, the lower side of the reaction chamber is closed by inserting and connecting the tip of the small diameter portion to the second cap. That is, when the first cap is moved by the lower end portion of the nozzle, it is a horizontal moving means for moving the nozzle to a position where the nozzle raising / lowering moving means and the second cap are arranged.
[0120]
According to the twenty-fourth invention, by sealing the reaction chamber, a highly reliable reaction and measurement thereof can be performed in a state where gas is excluded. In addition, the liquid can be introduced quickly and efficiently.
[0121]
25th invention has 1 or 2 or more reaction containers, and 1 or 2 or more liquid introducing | transducing parts which can connect this reaction container so that attachment or detachment is possible, The said reaction container has an opening part and has liquid. A storage chamber, a reaction chamber formed thinner or thinner than the storage chamber, and a container having at least one flow path communicating between the storage chamber or the outside and the reaction chamber, A heating / cooling unit that enables heating or cooling of the one or more reaction chambers and an optical information measurement unit that obtains optical information in the one or more reaction chambers; This is a liquid introduction reaction measuring device that causes a reaction with respect to the liquid introduced into the liquid and measures its optical information.
[0122]
Here, the surface of the reaction chamber that heats or cools the reaction chamber, the surface that receives light from the reaction chamber, and the surface that irradiates light to the reaction chamber are different from the same case. There can be.
The optical information measurement unit is provided with at least one light receiving end for receiving light from the reaction chamber in contact with or close to the reaction chamber. When the luminescent material is a fluorescent material or the like, it has one or more irradiation end portions that irradiate excitation light for generating fluorescence.
Moreover, it is preferable that it can move relatively between the reaction chamber of the reaction container connected to the liquid introduction part and the heating / cooling part or / and the optical information measuring part. This can facilitate or facilitate the automation of the process.
[0123]
According to the twenty-fifth invention, heating and cooling are performed by the heating / cooling section provided in contact with or in proximity to the reaction chamber of the reaction vessel. Therefore, since a metal block or the like is not required, the temperature of the liquid contained in the container is controlled with high accuracy and faithful response with respect to the liquid that is thinned or thinned in a state where no gas or bubbles are mixed. Will be able to.
Also, by heating or cooling the thinned or thinned liquid in the absence of gas or bubbles, the time from when the heating or cooling instruction is given until the liquid temperature is evenly distributed can be shortened. The processing can proceed quickly.
[0124]
Furthermore, since the optical information in the reaction chamber is measured in a state where no gas or bubbles are mixed, highly accurate optical information can be obtained.
[0125]
In particular, if the liquid is heated or cooled so that the heating and cooling unit is sandwiched from both sides along the thickness direction, the liquid can be heated or cooled more quickly and efficiently.
[0126]
A twenty-sixth aspect of the present invention is the liquid introduction reaction measuring device further comprising a sealing means for sealing the reaction chamber of the reaction vessel.
[0127]
Here, as the sealing means, for example, when a part or all of the flow path or reaction chamber of the reaction vessel is formed of a deformable soft member, the reaction chamber is deformed by the soft member. When the reaction chamber is a gap between the inner surface of the pipette tip and the outer surface of the core accommodated in the tip, the first cap and the second cap And a moving means for moving the first cap downward, moving the pipette tip to the position of the second cap, and connecting the second cap to the lower end of the tip. . In addition, as the pressing portion, a protrusion provided at a light receiving end described later, or Optical information measuring unit There is a protrusion provided on the end face of the irradiation end. In addition, as the sealing means, ultrasonic radiation means or welding means by high frequency, laser, heat generation, or the like corresponds to this.
[0128]
According to the twenty-sixth invention, by sealing the reaction chamber, a highly reliable reaction and measurement thereof can be performed in a state where the gas is excluded. In addition, the liquid can be introduced quickly and efficiently.
[0129]
In a twenty-seventh aspect of the invention, the optical information measuring unit includes one or more irradiation end portions for irradiating the reaction chamber with light, and one or more light receiving end portions for receiving light from the reaction chamber. The irradiation end portion is provided in contact with or close to the largest wall surface of at least one of the plurality of wall surfaces surrounding the reaction chamber, and the light receiving end portion is at least one excluding the largest wall surface. The liquid introduction reaction measuring device provided in contact with or in proximity to the wall surface.
[0130]
According to the twenty-seventh aspect, by irradiating light on the wall surface having the largest area, it is possible to irradiate the entire reaction chamber with a sufficient amount of light, so that optical information can be obtained efficiently.
[0131]
The twenty-eighth invention is The optical information measuring unit is It has one or two or more irradiation end portions for irradiating light to the reaction chamber, and one or two or more light receiving end portions for receiving light from the reaction chamber, and the irradiation end portion and the light receiving end portion are The liquid introduction reaction measuring device provided in contact with or in proximity to one of the plurality of walls surrounding the reaction chamber.
[0132]
According to the twenty-eighth aspect, since the irradiation end portion and the light receiving end portion are provided on one wall surface of the reaction chamber, a compact configuration can be achieved and the number of parts can be reduced.
[0133]
In a twenty-ninth aspect of the invention, the optical information measuring unit includes one or more irradiation end portions for irradiating the reaction chamber with light, and one or more light receiving end portions for receiving the light from the reaction chamber. The heating / cooling unit has a heating / cooling end for heating or cooling provided in contact with or close to the reaction chamber, and an irradiation end of the optical information measurement unit and the heating / cooling end The unit is a liquid introduction reaction measuring device provided in contact with or close to one of the plurality of wall surfaces surrounding the reaction chamber.
[0134]
Here, the “heating / cooling end” refers to the case where either one heating end or cooling end provided separately is used in addition to the case where one end performs heating and cooling like a Peltier element. Or both the heating end and the cooling end.
[0135]
According to the twenty-ninth invention, by providing the heating / cooling end portion and the irradiation end portion on one wall surface, the apparatus scale can be reduced and the device can be efficiently arranged.
[0136]
A thirtieth aspect of the invention is a liquid introduction reaction measuring device in which a heating element or a cooling body of the heating / cooling unit is provided at the irradiation end.
[0137]
For example, the irradiation end is an optical system such as a rod lens, other lenses, or a transparent body, and the heating element is a resistance line such as a nichrome wire, and an optical element such as a rod lens. There is a case where it is wound around a system or a heating element is enclosed in an optical system such as the rod lens.
[0138]
Alternatively, a multi-layered photosensitive heat generating glass incorporated in an optical system such as the rod lens may be used. Thereby, a light-cooling end portion for heating and cooling, an end portion for heating, or an end portion for cooling can be provided.
[0139]
According to the thirtieth aspect, since the rod lens can be used as the heating / cooling end by providing the rod lens with the heating / cooling end, the apparatus scale can be reduced and the narrow space around the reaction vessel can be effectively used. Can be used.
[0140]
In a thirty-first aspect of the present invention, the heating / cooling unit is a heating end for heating or a cooling end for cooling provided in contact with or in proximity to the reaction chamber, and the heating end or cooling end The unit is a liquid introduction reaction measuring device provided in contact with or in proximity to the one wall surface having the largest area among the plurality of wall surfaces surrounding the reaction chamber. Here, you may make it provide the said irradiation edge part in the said wall surface with the said edge part for heating. For example, the case where the heating end and the irradiation end are connected corresponds to such a case.
[0141]
According to the thirty-first aspect, heating and cooling can be efficiently performed by providing the heating end or the cooling end on the wall surface having the largest area among the walls surrounding the reaction chamber.
[0142]
In a thirty-second invention, the heating / cooling section has a heating / cooling end for heating or cooling, and the heating / cooling end is provided so as to be able to contact and separate relative to the reaction vessel. It is a liquid introduction reaction measuring device.
By controlling the position of the heating and cooling end with respect to the reaction vessel, the reaction chamber can be brought into contact with, brought close to, or separated from the reaction chamber, thereby changing the heat conduction efficiency.
“Providing the heating / cooling end portion to be contactable / separable” means that the heating / cooling end portion is provided to be contactable / separable, or only the heating end portion is provided to be contactable / separable. There may be a case where only the portion is provided so as to be able to contact and separate, and a case where the heating end portion and the cooling end portion are provided so as to be able to contact and separate.
[0143]
According to the thirty-second invention, by controlling the position of the heating / cooling end with respect to the reaction vessel, the reaction chamber can be brought into contact with, brought close to, or separated from the reaction chamber, thereby changing the heat conduction efficiency. Therefore, efficient and highly accurate temperature control can be performed.
[0144]
In a thirty-third aspect of the present invention, the heating / cooling section is provided with either a heating end portion for heating or a cooling end portion for cooling in each of a plurality of regions, and any one of a plurality of types in advance for each region. Provide a defined temperature,
A liquid introduction reaction measuring device provided between the reaction chamber connected to the liquid introduction part and the heating end or the cooling end so as to be relatively movable so as to approach or come into contact with each other. is there.
[0145]
As a result, the temperature setting in a predetermined order can be replaced with the movement control of the order of passing through the area where the corresponding temperature is provided, the movement path, and the residence time of each area. At this time, each of the plurality of regions is sequentially arranged, for example, in a horizontal shape, a vertical shape, a circumferential shape, or a zigzag shape, in accordance with the setting order of a plurality of types of temperatures to be set in the reaction chamber. They are arranged at intervals apart so as not to affect the temperature. This makes it possible to efficiently control the temperature while minimizing the moving distance along the moving path relative to the region of the reaction chamber.
[0146]
Moreover, since it is relatively movable, it may be provided so that both the liquid introduction unit and the heating / cooling unit move. For example, the movement between the regions is performed by the liquid introduction unit, The heating end or cooling end may be provided so as to be movable toward and away from the reaction chamber. In addition, as an example of several types of temperature, it is the temperature set, for example when performing PCR. The relative moving means between the liquid introduction part and the heating end or cooling end is a means for moving the liquid introduction part in the vertical direction or the horizontal direction, or the heating end. Or there may be means for moving the cooling end, or a combination of both. Moreover, as a heating edge part or a cooling edge part, there may be a case where only a predetermined temperature can be provided, or a case where various temperatures can be set per se. Further, the region where a certain temperature is set may be formed of two separate parts, each being provided at a position facing each other so as to sandwich the moving path of the reaction chamber.
[0147]
According to the thirty-third aspect, the setting to various temperatures can be performed by relative movement of the reaction vessel with respect to the region by the liquid introduction unit. Therefore, since temperature control can be replaced with movement control between the reaction chamber and the region, it is possible to simplify and unify processes at the same level as various reagent and liquid transfer processes. In addition, the energy efficiency is higher than when the temperature control is performed by raising and lowering the temperature of a heating element such as an aluminum block having a large heat capacity with respect to the reaction vessel and the temperature of the cooling element. In addition, compared to heating and cooling control of a heating element or cooling body such as an aluminum block with a large heat capacity, it can move instantaneously to a different temperature range, so the relaxation time until the temperature stabilizes is shortened, High-precision and fine-grained temperature control can be performed.
[0148]
In a thirty-fourth aspect of the present invention, a temperature corresponding to the arrangement is set across the movement path direction at intervals between adjacent areas arranged along the movement path direction relative to the area of the reaction chamber. It is the liquid introduction | transduction reaction measuring apparatus provided with the gas injection part which injects the gas of.
[0149]
In particular, when the temperature of the reaction chamber is changed to a temperature lower than a temperature set in a certain stage, the low temperature gas is injected at an interval between the adjacent regions. Thus, the set temperature can be lowered smoothly. The gas injection unit also includes a blower. The gas injection unit is included in the heating / cooling unit. The “movement path direction” is, for example, a horizontal direction, a vertical direction, or a direction along the circumference. For example, a gas cylinder is used as the gas injection unit.
[0150]
According to the thirty-fourth aspect, by smoothly injecting a gas at a predetermined temperature between adjacent regions where a plurality of temperatures are set along the relative movement path, the temperature transition is smoothly performed, and the adjacent regions The influence of the mutual temperature between them can be cut off.
[0151]
In a thirty-fifth aspect of the present invention, the optical information measuring unit has the light receiving end, and the reaction chamber connected to the liquid introducing unit and the light receiving end are relatively close to each other so as to approach and contact each other. The liquid introduction reaction measuring device is provided so as to be movable and receives light from the reaction chamber.
[0152]
Here, the region where the light receiving end portion is provided is preferably arranged in the processing order along the relative movement path of the reaction chamber with respect to the region including the region where the heating and cooling unit is provided. . For example, when the measurement is performed after setting the temperature, it is provided so as to be positioned after the last temperature setting region along the movement path.
[0153]
According to a thirty-fifth aspect of the invention, the liquid introduction part is relatively movable with respect to the light receiving end part of the optical information measuring part, and the light receiving end part is provided along the relative movement path. Yes. Therefore, the processing can be efficiently performed by associating the processing procedure with the arrangement of each region. In addition, since temperature control and optical information measurement can be performed by the same movement control, the control is simplified.
[0154]
In a thirty-sixth aspect of the invention, the optical information measuring unit has one or more irradiation end portions for irradiating light to the reaction chamber, and the irradiation end portion is provided so as to be able to contact and separate from the reaction container. This is a liquid introduction reaction measuring device.
By controlling the position of the irradiation end with respect to the reaction vessel, efficient light irradiation is performed, and when the irradiation end and the heating end are connected, heat conduction or heat It is possible to perform control such as shutting off.
[0155]
According to the thirty-sixth aspect of the present invention, when the irradiation end and the heating end are connected to each other by controlling the position of the irradiation end with respect to the reaction vessel, the light is efficiently irradiated. In this case, heat conduction and heat insulation can be performed. Therefore, efficient and highly accurate temperature control and light irradiation can be performed.
[0156]
In a thirty-seventh aspect of the invention, the heating / cooling unit has a cooling end for cooling, and the cooling end is a liquid introduction reaction measuring device which is a blower for blowing air toward the reaction vessel.
Thus, particularly when the heating end and the irradiation end are separated from the reaction vessel, heat is radiated from the reaction chamber by feeding air with the blower, and heat can be controlled efficiently.
[0157]
According to the thirty-seventh aspect of the invention, particularly when the reaction chamber is cooled by separating the heating end and the irradiation end from the reaction vessel, heat release from the reaction chamber is promoted by sending air by the blower. And heat control can be performed efficiently.
[0158]
In a thirty-eighth aspect of the invention, the reaction chamber of the reaction vessel is formed in a cylindrical shape, surrounded by two disk-like large walls and a small side wall, and receives light traveling in the radial direction of the cylinder 1 Alternatively, it is a liquid introduction reaction measuring device provided with two or more light receiving ends.
In addition, when providing an irradiation end surface in the said reaction chamber, it provides so that light may be irradiated to the said radial direction.
[0159]
According to the thirty-eighth aspect, by forming the reaction chamber in a substantially cylindrical shape, uniform light information can be obtained by irradiating or receiving light on the side surface.
[0160]
In a thirty-ninth aspect of the present invention, the optical information measurement unit includes two or more irradiation end portions provided at the irradiation positions of the reaction chambers of the two or more reaction vessels, and a plurality of lights each generating light having a plurality of types of wavelengths. A type of light source, a light source selection unit that switches and selects one type of light among the light from the light source in time, and guides the light to all the irradiation ends at once, and two or more of the reaction vessels Two or more light receiving end portions provided at each light receiving position of the reaction chamber, a light receiving position selecting portion for selecting light from each light receiving end portion by time switching, and light from the selected light receiving position passes An optical filter selection unit that selects a plurality of types of optical filters to be switched in terms of time, and a photoelectric element that sequentially inputs light from a selected light receiving position and passing through the selected optical filter It is a liquid introduction reaction measuring device.
[0161]
Here, a plurality of types of optical filters are provided, for example, in order to label a DNA fragment or the like whose amount or concentration is to be measured in real-time PCR or the like in the reaction chamber. This is the case where a labeling substance that outputs is used. Accordingly, the presence or amount of the corresponding labeling substance can be measured by transmitting light having each wavelength through the optical filter.
[0162]
The “photoelectric element” is an electronic element utilizing the photoelectric effect, and includes a photoelectric tube, a photomultiplier tube, a photoconductive cell, a phototransistor, a photodiode, and the like.
Note that light irradiation is necessary to emit light by irradiating the fluorescent material or the like that may exist in the reaction chamber with excitation light.
[0163]
According to the 39th invention or the 40th invention, even if two or more labeling substances are used for two or more reaction vessels, the reaction chamber and the labeling substance are temporally targeted. Since processing can be performed using a small number of photoelectric elements by switching the type of the labeling substance, the overall apparatus scale can be reduced or simplified.
[0164]
In a fortieth aspect of the invention, the optical information measuring unit includes two or more irradiation end portions provided at the irradiation positions of the reaction chambers of the two or more reaction vessels, and a plurality of lights each generating a plurality of types of wavelengths. A light source irradiation position selection unit that temporally switches and selects one type of light from the light sources, and switches the selected light temporally to guide each light receiving end. An optical device that selects two or more light receiving end portions provided at each light receiving position of the reaction chamber of the two or more reaction vessels and a plurality of types of optical filters through which light from the light receiving position is to be switched by temporal switching. It is a liquid introduction reaction measuring device including a filter selection unit and a photoelectric element that sequentially inputs light that has passed through a selected optical filter.
[0165]
In a forty-first aspect of the invention, the optical information measuring unit includes an irradiation end that irradiates light to the reaction chamber of the reaction vessel, and a light receiving end that receives light from the reaction chamber, and the light receiving end. The light receiving direction and the opening angle of the reaction chamber with respect to the reaction chamber are outside the incident and reflection paths determined based on the irradiation direction of the irradiation end portion and the shape of the reaction chamber, so that the light receiving end portion receives light from the reaction chamber. Is a liquid introduction reaction measuring device defined in the above.
[0166]
The irradiation end portion and the light receiving end portion correspond to, for example, an optical system such as a rod lens or a fiber tip. For example, the irradiation end portion is provided in a region facing the region where the light receiving end portion is provided and a moving path along which the reaction chamber having translucency moves. In this case, the optical axis of the irradiation end and the optical axis of the light receiving end, or the rod lens or the fiber of the fiber so that the incident angle to the reaction chamber and the transmission angle from the reaction chamber form a predetermined finite angle. It is possible to increase the accuracy of optical information measurement by tilting the optical system such as the tip by the above angle or using fiber, rod, glass to reduce the influence of the irradiation end on the light receiving end. it can. The positions of the irradiation end and the light receiving end with respect to the reaction chamber are positioned so as to sandwich the small wall surface when positioned so as to sandwich the large wall surface of the reaction chamber. If or. May be located on the same wall.
[0167]
In a forty-second aspect of the invention, there are provided one or two or more rotatable rotating bodies, one or more containers formed so as to be detachably connectable to the rotating bodies, and a rotation driving unit that rotationally drives the rotating bodies. The container has an opening and a storage chamber capable of storing the liquid, and a medium communicating with the storage chamber and capable of passing the liquid and performing a predetermined operation on the liquid. A working chamber provided so as to block the passage path of the liquid, and the working chamber is formed farther from the rotation axis of the rotating body than the storage chamber, and is accommodated in the storage chamber. A liquid introducing device for introducing the liquid into the working chamber.
[0168]
The container may be connectable to the rotating body via a cap.
Here, as the “medium”, there are a stationary phase of a filter and a column which will be described later. Filters are used to separate a given substance in a liquid by passing it through a number of penetrating pores or voids of a given size (pore diameter or average void diameter or length) or adsorption Including the case of separation by. In addition, when the rotating shaft line of the said rotary body penetrates the said container, it corresponds to autorotation and the whole apparatus scale can be made small. Thus, for example, it can be used for extraction and purification of various biological substances such as nucleic acids, oligonucleotides, and proteins.
[0169]
In a forty-third aspect of the invention, the rotating body is a rotatable nozzle that can suck and discharge gas, and the nozzle has a rotation axis along the axial direction thereof.
[0170]
A forty-fourth aspect of the invention is a liquid introducing device, wherein the medium is a filter having a predetermined pore diameter.
[0171]
In a forty-fifth aspect of the present invention, the working chamber includes a filter chamber having the filter communicated with the storage chamber, and a storage chamber that is communicated with the filter chamber and is detachably attached to the filter chamber, The liquid introduced into the filter chamber by the rotation of the rotator passes through the filter and reaches the storage chamber.
[0172]
Here, the material that has passed through the filter is accommodated in the accommodation chamber. The storage chamber and the filter chamber are connected by an attachment member such as a screw, for example.
[0173]
In a forty-sixth aspect of the invention, the medium is a predetermined stationary phase, and the working chamber has a column in which the medium is stored and a storage chamber that is connected to the column and is detachably attached to the column. The liquid introduced into the column by the rotation of the rotating body can pass through the column and reach the storage chamber.
[0174]
Here, the “stationary phase” may be solid or liquid. The column is used, for example, to separate the sample mixture by moving the sample mixture to the column with an appropriate developing agent (mobile phase) and using the difference in the moving speed based on the difference in the adsorptivity of each component and the distribution coefficient.
[0175]
A forty-seventh aspect of the present invention is the liquid introducing device, wherein the working chamber is formed thinner or narrower than the storage chamber.
[0176]
According to the forty-second invention, the forty-fourth invention, the forty-fifth invention, the forty-sixth invention or the forty-seventh invention, various containers having at least a storage chamber and a working chamber located far from the rotation axis are used as the rotating body. By connecting and rotating, under the atmospheric pressure, the passage of the liquid can be facilitated by utilizing the centrifugal force even when the passage of the liquid to the medium provided in the working chamber is difficult. Various treatments can be performed by connecting various containers and introducing the liquid. Further, if the liquid is introduced by the rotation of the container, the work area can be reduced and the processing can be efficiently performed as compared with the case of using the revolution. In particular, by using a filter having a function of extracting or purifying nucleic acid, protein or the like as the medium, it is possible to extract or purify biological substances such as nucleic acid or protein. Then, by combining with the PCR process, it is possible to consistently perform processes such as extraction, amplification, expression, and purification for nucleic acids, proteins, and the like. According to the forty-fourth or forty-fifth aspects of the present invention, by providing a detachable storage chamber in the work chamber, it is easy to handle because the liquid subjected to the predetermined work can be collected and easily taken out. According to the forty-sixth aspect of the present invention, it is possible to efficiently perform a process of adding a predetermined work to the liquid and thinning or thinning the liquid on which the work has been added.
[0177]
According to the forty-third aspect, a rotatable nozzle is used as the rotating body. Accordingly, not only centrifugal force but also suction / discharge pressure can be used, so that liquid can be dispensed into the storage chamber. Further, depending on the shape of the container, the suction / discharge pressure can be used to introduce the liquid into the reaction chamber, so that various processes can be performed consistently.
[0178]
The forty-eighth aspect of the invention is the step of storing the liquid to be treated in the storage chamber of the reaction container according to the first to seventeenth inventions, and introducing the liquid from the storage chamber into the reaction chamber of the reaction container. A step of closing an opening or flow path provided in the reaction chamber to seal the liquid in the reaction chamber, a step of heating and cooling the liquid sealed in the reaction chamber, and a step from the reaction chamber A liquid introduction reaction measuring method including a step of measuring optical information.
[0179]
Here, the “liquid” includes, for example, a target substance such as a nucleic acid and necessary reagents. “Accommodating” is performed using, for example, a dispensing device. “Introduction” is performed, for example, by connecting the reaction vessel to a nozzle that is the liquid introduction unit and rotating the reaction vessel, or by using a suction / discharge mechanism of a dispensing device that is the liquid introduction unit.
[0180]
According to the forty-eighth aspect of the invention, heating and cooling are performed by a heating / cooling section provided in contact with or in proximity to the reaction chamber of the reaction vessel. Therefore, since a metal block or the like is not required, the temperature of the liquid contained in the container is controlled with high accuracy and faithful response with respect to the liquid that is thinned or thinned in a state where no gas or bubbles are mixed. Will be able to. Also, by heating or cooling the thinned or thinned liquid in the absence of gas or bubbles, the time from when the heating or cooling instruction is given until the liquid temperature is evenly distributed can be shortened. The processing can proceed quickly. In addition, according to the present invention, a series of processes can be automated using the reaction vessel.
[0181]
Furthermore, since the reaction chamber is sealed and the optical information in the reaction chamber is measured in a state where no gas or bubbles are mixed, highly accurate optical information can be obtained.
[0182]
In particular, if the liquid is heated or cooled so that the heating and cooling unit is sandwiched from both sides along the thickness direction, the liquid can be heated or cooled more quickly and efficiently.
[Brief description of the drawings]
[0183]
FIG. 1 is a view showing a reaction vessel according to a first embodiment of the present invention.
FIG. 2 is a perspective view showing a reaction container and a cap according to the first embodiment of the present invention.
FIG. 3 is an explanatory diagram of a reaction vessel according to the first embodiment of the present invention.
FIG. 4 is a partially enlarged perspective view of the reaction vessel according to the first embodiment of the present invention.
FIG. 5 is a view showing a reaction vessel according to a second embodiment of the present invention.
FIG. 6 is a view showing a reaction vessel according to a third embodiment of the present invention.
FIG. 7 is a view showing a reaction vessel according to a fourth embodiment of the present invention.
FIG. 8 is a cross-sectional view of a reaction vessel according to a fourth embodiment of the present invention.
FIG. 9 is a diagram showing a case where a reaction container according to a fifth embodiment of the present invention is connected to a nozzle and reaction measurement is performed.
FIG. 10 is a diagram showing a case where reaction vessels according to sixth to eighth embodiments of the present invention are connected to a nozzle and reaction measurement is performed.
FIG. 11 is a view showing a reaction vessel according to a ninth embodiment of the present invention.
FIG. 12 is a cross-sectional view and an exploded view of a reaction vessel according to a ninth embodiment of the present invention.
FIG. 13 is an overall view showing a reaction measurement processing system according to an embodiment of the present invention.
FIG. 14 is a side view showing a liquid introduction apparatus according to an embodiment of the present invention.
FIG. 15 is a diagram showing a filter built-in chip, a filter built-in container, and a column connection container according to an embodiment of the present invention.
FIG. 16 is a diagram illustrating an example of a trigger light source and a light receiving unit according to the embodiment of the present invention.
FIG. 17 is a diagram illustrating an example of a trigger light source and a light receiving unit according to another embodiment of the present invention.
FIG. 18 is a diagram illustrating an example of a rod lens according to an embodiment of the present invention.
FIG. 19 is a view showing a rotation mechanism according to an embodiment of the present invention.
FIG. 20 is a view showing a reaction vessel according to a tenth embodiment of the present invention.
FIG. 21 shows a PCR unit according to an embodiment of the present invention.
FIG. 22 is a process flowchart according to the embodiment of the present invention.
BEST MODE FOR CARRYING OUT THE INVENTION
[0184]
According to the present invention, by introducing the homogenized suspension into the reaction chamber of the reaction vessel using centrifugal force or pressure, the liquid can be diluted easily, reliably and homogeneously without mixing bubbles or gas. By realizing layering or capillary sealing, the accuracy and responsiveness of temperature control of the liquid was improved, and for example, processing such as measurement of the amount in real-time PCR was made faster and more efficient.
[0185]
Next, embodiments of the present invention will be described with reference to the drawings. This embodiment should not be construed as limiting the present invention unless otherwise specified. Moreover, the same thing in each Example was represented by the same code | symbol, and description was abbreviate | omitted.
[0186]
1A, 1B, and 1C are a perspective view, a side view, and a front view showing a reaction vessel 11 according to a first embodiment of the present invention. In FIGS. 1A and 1C, in order to clearly show the inside, the transparent film 18 which is a soft member forming a part of the transparent film 18 is removed.
[0187]
As shown in FIG. 1 (a), the reaction vessel 11 has an opening 13 at the top, a cylindrical storage chamber 12 capable of storing a liquid, the storage chamber 12, a liquid introduction channel 16 and It has a reaction chamber 15 that is communicated through the exhaust passage 17 and formed thinner than the storage chamber 12, the liquid introduction passage 16, and the exhaust passage 17, and the liquid introduction passage. 16, the exhaust flow path 17 and the reaction chamber 15 are formed in a substantially layered shape with the gas flow passage 17 and the reaction chamber 15 therebetween, and the whole is provided in the translucent reaction section 14. The reaction vessel 11 according to the present embodiment corresponds to the fluid circuit because the reaction chamber 15 communicates with the liquid introduction flow path 16 and the exhaust flow path 17. The opening 13 can be connected by inserting a cap 20 described later, and the cap 20 can be connected to a nozzle 22 described later as a rotating body by screwing. Accordingly, the opening 13 can be connected to the nozzle 22 through the cap 20. That is, the reaction vessel 11 belongs to the class of introducing a liquid by applying a centrifugal force using a rotating body as a liquid introduction part for introducing a liquid into the reaction chamber 15.
[0188]
The reaction chamber 15 is provided below the storage chamber 12 and at a position farther as the position coordinate of the center of gravity of each chamber than the storage chamber 12 with respect to the axis of the opening 13 or the storage chamber 12. . The axis of the opening 13 or the storage chamber 12 coincides with the rotation axis of the rotating body when the reaction vessel 11 is connected to a nozzle 22 as a rotating body described later.
[0189]
Therefore, when the rotating body is rotated, centrifugal force is applied to the liquid in the storage chamber 12 and the liquid is introduced into the reaction chamber 15 at a position farther from the rotation axis. A part of the reaction chamber 15, the liquid introduction flow path 16, and the exhaust flow path 17 are provided in a flat frame 14a having a bottomed groove, and one side of the frame 14a will be described later. It is blocked by the film 18. The liquid introduction channel 16 has an inlet on the inner surface of the storage chamber 12 and an outlet on the upper portion of the reaction chamber 15, and the exhaust channel 17 has an inlet on the lower portion of the reaction chamber 15. The reaction chamber 15 and the storage chamber 12 are communicated with each other with an outlet on the inner bottom surface of the storage chamber 12.
[0190]
The liquid introduction flow path 16 has an elastic valve body 16a as an elastic block member formed of an elastic body, and the liquid introduction flow path 16 can be closed by pressing the elastic valve body 16a. . In addition, the exhaust channel 17 can be closed by pressing the membrane 18 a little distance and a slant passage 17a that communicates with the lower portion of the reaction chamber 15 and that travels in a slanting upward direction. A hole 17b protruding to the side and an outlet 17d provided at the inner bottom of the storage chamber 12 are provided.
[0191]
As shown in FIG. 1 (b), the exhaust flow path 17 has a vertical path 17c that fluidly connects in the vertical direction parallel to the cylindrical axis of the storage chamber from the hole 17b to the outlet 17d. The vertical path 17c is provided so as to slightly protrude from the side of the planar frame 14a where the bottom surface of the reaction chamber 15 and the like is provided. Further, the side surface of the frame 14a facing the up-and-down path 17c, that is, the opening side of the reaction portion 14 is attached with the film 18 to the frame 14a by adhesion or the like so as to close the opening. 15 and the openings of the flow paths 16 and 17 are closed. The film 18 is formed of a soft member such as polyethylene or silicone that is easily deformed by pressing. Therefore, the reaction chamber 15 is surrounded by a plurality of wall surfaces. During the reaction, the bundle of fibers provided with the pressing portions 101 and 102 is provided outside the wall surface on which the film 18 is provided. A rod lens 75 for irradiating light from a trigger light source 71 that generates excitation light is disposed on the opposite wall surface. Here, a resistance wire of a heating element 79 is wound around the rod lens 75 so that the rod lens 75 functions as a heating end. The light receiving end 78 and the rod lens 75 are provided so as to be able to contact and separate from the large wall surface of the reaction chamber 15.
[0192]
By providing a part of the exhaust passage 17 close to and parallel to the axis, introduction of liquid through the exhaust passage 17 is reduced by centrifugal force when the reaction vessel 11 is rotated about the axis.
[0193]
As shown in FIG. 1C, the elastic valve body 16a of the liquid introduction channel 16 has a hole 16b and a gap 16c that can be pressed and closed, as will be described later. The upper inner surface 19 of the storage chamber 12 has an inner diameter that allows a cap 20 to be described later to be fitted. A flange 12 a for detaching the reaction vessel 11 is provided on the outer surface of the storage chamber 12. In addition, the light from the reaction chamber 15 in which a fluorescent substance or the like that emits light when irradiated with the excitation light is accommodated is different from FIG. 1B, for example, from one of the wall surfaces surrounding the reaction chamber. Received light. In this example, light is received from the light receiving end located on a predetermined small wall surface and guided to the light receiving unit 72 through the optical fiber.
[0194]
FIG. 2A is a perspective view showing the reaction vessel 11 and the cap 20 to be connected to the reaction vessel 11.
[0195]
The cap 20 is a hollow cylindrical member that is fitted and connected to the opening 13 of the storage chamber 12 of the reaction vessel 11. The cap 20 has three kinds of annular protrusions that come into contact with the inner surface of the opening 13, and from the bottom are airtight rims 20a and 20b and a lock rim 20c. The inner surface of the cap 20 is a nozzle fitting portion 20d that fits with a nozzle (not shown). In addition, a plurality of protrusions 20e are provided on the outer surface of the cap 20 along the axial direction of the cap 20, and can be engaged with cap engaging portions 47a and 47b described later. Desorption is possible.
[0196]
FIG. 2B shows a state in which the cap 20 is fitted and connected to the reaction vessel 11.
[0197]
FIG. 3A shows a front perspective view of the state in which the cap 20 is fitted and connected to the opening 13 in order to show the reaction vessel 11 in more detail. Reference numeral 14b in the figure is a shallow depression provided in the frame 14a. A cross-sectional view taken along the line AA is shown in FIG. This figure shows a state in which the airtight rims 20a and 20b and the locking rim 20c of the cap are in contact with the inner surface of the upper portion of the storage chamber 12. The vicinity of the hole 17b provided in the lower part of the vertical path 17c is shown in an enlarged manner in FIG. Since the hole 17b protrudes toward the film 18 and is provided close to the film 18 with a certain distance, the hole 17b is pressed by the film 18 by pressing the film 18 from the outside. As a result, the exhaust passage 17 is closed.
[0198]
FIG. 3C shows the main part of the cross section cut along the CC line in FIG. This portion shows the liquid introduction flow channel 16 provided with the elastic valve body 16a, and is provided between the frame 14a and the membrane 18. The elastic valve body 16a is formed of the hole 16b and a gap 16c communicating with the hole 16b, and presses the gap 16c, as will be clearer when referred to in conjunction with FIG. Thus, the liquid introduction flow path 16 can be closed by closing the gap 16c. Thereby, the liquid introduced into the reaction chamber 15 can be sealed in the reaction chamber 15.
[0199]
FIG. 5 shows a reaction vessel 11a according to the second embodiment. Unlike the reaction vessel 11 described above, the reaction vessel 11a is provided with a rotation support shaft 14c along the axis of the opening 13 of the storage chamber 12 on the lower side of the reaction unit 14 of the reaction vessel 11a, so that the core during rotation is provided. Can prevent shakes.
[0200]
Subsequently, a reaction vessel belonging to a class for introducing a liquid by suction and discharge of a nozzle will be described with reference to FIGS. 6 and 7.
[0201]
FIG. 6 shows a reaction vessel 31 according to the third embodiment.
6 (a) shows a perspective view of the reaction vessel 31, FIG. 6 (b) is a front view thereof, FIG. 6 (c) is a sectional side view thereof, and FIG. FIG. 6C is an enlarged cross-sectional view of the region F shown in FIG. 6C, and FIG. 6E is an enlarged perspective view of a part of the region F shown in FIG.
[0202]
The reaction vessel 31 is provided on a lower side of the reaction chamber 33, a cylindrical storage chamber 32 having a large diameter, a rectangular columnar reaction chamber 33 having both bottom surfaces formed thinner than the storage chamber 32. And a narrow-diameter portion 34 formed thinner than the cylinder.
[0203]
The storage chamber 32 and the reaction chamber 33 and the reaction chamber 33 and the outside are connected to each other by a flow path 32c and a small diameter portion 34, respectively. Therefore, the reaction vessel 31 according to the present embodiment corresponds to the fluid circuit because the reaction chamber 33 communicates with the two flow paths. In addition, elastic valve bodies 35 and 36 that can be closed by pressing are provided at closed positions of the flow path 32c and the small diameter portion 34.
[0204]
A nozzle (not shown) can be fitted and connected to the storage chamber 32 at the opening 32a. The storage chamber 32 has, for example, the storage chamber below the connection portion of the nozzle. A heat insulating filter 32 b is provided so as to divide 32. Thereby, the heating and cooling effect on the reaction chamber 33 can be enhanced. The lower side of the storage chamber 32 is tapered and communicates with the flow path 32c. Further, a plurality of protrusions 32d are provided on the outer surface of the storage chamber 32, and the protrusions 32d can be automatically removed by a chip removal plate 23a described later.
[0205]
One of the large wall surfaces of the reaction chamber 33 is stretched with a film 37 formed of a soft member that can be deformed by pressing, and the other of the large wall surfaces is formed by the frame of the reaction vessel 31 and is thermally conductive. In order to increase the thickness, the frame covering the reaction chamber 33 is provided with a recess 38 to make it thin.
[0206]
As shown in FIG. 6E, the elastic valve bodies 35 and 36 have a hole 39 and a gap 40 that can be closed by pressing.
[0207]
FIG. 7 shows a chip-like reaction vessel 41 according to the fourth embodiment, a cap 42 through which a fluid can pass, and a liquid introduction device 50 that also serves as a reaction vessel liquid introduction device that can rotate, move up and down and move horizontally. 2 shows a reaction vessel connecting portion in which the chip-like reaction vessel 41 is connected to the nozzle 22.
[0208]
FIG. 7A is an exploded perspective view of the reaction vessel connecting portion of the liquid introducing device 50, and FIG. 7B shows the reaction vessel connecting portion of the liquid introducing device 50, and FIG. (E) shows the chip-like reaction when heating and cooling is performed using the liquid introduction device 50 to the region where the heat conduction blocks 49a and 49b serving as heating ends of the heating and cooling unit are provided. The automatic operation of detaching from and connecting to the container 41 from the liquid introducing device 50 is shown.
[0209]
As shown in FIG. 7 (a), the chip-like reaction vessel 41 is provided with a cylindrical large-diameter portion 45 and a small-diameter provided below the large-diameter portion 45 and formed thinner than the large-diameter portion 45. A portion 46, an opening 45 a provided on the upper side of the large-diameter portion 45, having an outer diameter larger than that of the large-diameter portion 45, and capable of inserting the tip end portion 42 b of the cap 42; And a cylindrical core 43 accommodated from the small diameter portion 46 to the small diameter portion 46. On the outer peripheral surface of the core 43, a plurality of protrusions 43a as spacers for forming a gap with the inner peripheral surface of the accommodated large diameter portion 45 or the small diameter portion 46 project outward. It is provided as follows. The gap between the outer peripheral surface of the core 43 and the inner peripheral surface of the large diameter portion 45 corresponds to the reaction chamber. The space above the core 43 above the large-diameter portion 45 corresponds to the storage chamber.
[0210]
The lower end of the core 43 is tapered to match the shape of the small diameter portion 46, and the upper end of the core 43 closes the tip end portion 42b of the cap 42 so that fluid cannot pass therethrough. It has the obstruction | occlusion part 43b which can do. In this example, the blocking portion 43b is formed in a conical shape corresponding to a hole portion 42f (see FIG. 8) that opens outward and is provided in the tip portion 42b of the cap 42.
[0211]
Further, the cap 42 is generally hollow and substantially cylindrical, and has a base portion 42a, a distal end portion 42b having an outer diameter smaller than the outer diameter of the base portion 42a, and an outer diameter of the base portion 42a. A fitting portion 42e having a thick outer diameter and capable of fitting the tip of the nozzle 22 is provided. The distal end portion 42b is provided with a rim 42c and an annular groove 42d that are in close contact with the inner surface of the opening 45a of the reaction vessel 41.
[0212]
As shown in FIGS. 7C to 7E, the reaction vessel 41 is moved to the heat conduction blocks 49a and 49b of the heating / cooling section by the liquid introduction device 50 connected to the nozzle 22. FIG. . Further, in order to scrape off the chip-like reaction vessel 41, the liquid introduction apparatus 50 is drilled slightly smaller than the outer diameter of the opening 45a and larger than the outer diameter of the base 42a of the cap 42. And a chip removal plate 23a having a semicircular cutout. The chip removal plate 23a is provided so as to be movable in the vertical direction and to be close to and away from the reaction vessel 41 and hence the axis of the nozzle 22. Further, the liquid introduction device 50 is provided with cap engaging portions 47a and 47b that can engage with the stepped portion of the fitting portion 42e of the cap 42 so as to sandwich the fitting portion 42e of the cap 42 from above and below. It has been. The lower cap engaging portion 47a has a semicircular cutout that is larger than the outer diameter of the base portion 42a of the cap 42 and smaller than the outer diameter of the fitting portion 42e, and the upper cap engaging portion 47a. The portion 47b has a semicircular cutout that is larger than the outer diameter of the nozzle 22 and smaller than the outer diameter of the fitting portion 42e. Further, the distance between the upper cap engaging portion 47a and the lower cap engaging portion 47b is fixed, and these cap engaging portions 47a and 47b are not only vertically moved but also the axis of the nozzle 22. It is provided so that it can approach and separate.
[0213]
FIG. 7 (c) shows that the chip-like reaction vessel 41 connected to the cap 42 is removed from the nozzle 22 by simultaneously lowering the cap engaging portions 47a and 47b and the chip removal plate 23a. The large diameter portion of the reaction vessel 41 is supported at a position sandwiched between the heat conduction blocks 49a and 49b. state Is shown.
[0214]
FIG. 7D shows a state in which only the chip removal plate 23 a is lowered while the cap 42 is connected to the nozzle 22, and the reaction vessel 41 is removed from the cap 42.
[0215]
FIG. 7E shows a state in which the reaction vessel 41 is sandwiched between the heat conduction blocks 49a and 49b in a state where the reaction vessel 41 is connected to the nozzle 22 via the cap.
[0216]
FIG. 8A is a cross-sectional view taken along a plane passing through the axis of the nozzle 22 in FIG.
As shown in an enlarged cross-sectional view of the reaction vessel 41 in FIG. 8B, a gap 41a surrounded by the outer surface of the core 43 and the inner surface of the large diameter portion 45 corresponds to the reaction chamber, A space 41b formed above the core 43 on the upper side of the large diameter portion 45 corresponds to the storage chamber. In addition, a hole 42 f having a shape that can be closed by the closing portion 43 b of the core 43 is formed in the distal end portion 42 b of the cap 42. The hole 42f is closed by the closing portion 43b in a state where the tip portion 42b is inserted deepest into the opening 45a of the reaction vessel 41. A heat insulating filter 42g is provided on the upper side inside the tip end portion 42b to prevent heat from the reaction chamber from being transferred to the nozzle 22. That is, the reaction vessel 41 according to the present embodiment corresponds to the fluid circuit because two openings are provided in the reaction chamber.
[0217]
FIG. 8C shows that the tip 42b of the cap 42 is hooked on the fitting portion 42e of the cap 42 by moving the cap engaging portions 47a and 47b upward, and the cap 42 is moved upward. Move slightly. Then, the closed portion 43b of the core 43 is removed from the hole portion 42f, and the nozzle 22 communicates with the reaction vessel 41 through the heat insulating filter 42g of the cap 42. Therefore, the small diameter portion 46 of the reaction vessel 41 is inserted into the vessel containing the liquid, and the gas is sucked by the nozzle 22 while the cap 42 is open with the hole portion 42f opened. Then, the liquid is introduced to the space portion 41b through the narrow diameter portion 46 of the reaction vessel 41 and the gap portion 41a. Thereafter, the tip 42b of the cap 42 is inserted into the opening 45a of the reaction vessel most deeply, the hole 42f is closed by the closing part 43b, and the tip of the small diameter part 46 is not shown. By inserting and fitting into another cap, the liquid can be sealed in the gap 41a.
[0218]
FIG. 9 shows an example of a reaction vessel 211 according to the fifth embodiment, in which the liquid introduction apparatus 50 is connected to a lower end portion of the nozzle 22 as a rotating body of the liquid introduction apparatus 50 via a cap 20. 50 is wound around the rod lens 75 as the irradiation end of the optical information measuring unit when it is transferred to the reaction measurement position, and the light receiving end 78 corresponding to the tip of the optical fiber and the rod lens 75, for example. The positional relationship with the elongated heating element 79 of the heating and cooling unit is shown. 9 and 10, the cap 20, the elastic valve body and the like are conceptually represented. The rod lens 75 around which the heating element 79 is wound is an irradiation end portion and corresponds to a heating end portion.
[0219]
FIG. 9A is a front sectional view showing the reaction vessel 211. The reaction vessel 211 communicates with the storage chamber 212 having an opening and capable of storing a liquid, A reaction chamber 215 having a substantially triangular prism shape that is formed thinner than the storage chamber 212 and an exhaust passage 217 that communicates between the storage chamber 212 and the reaction chamber 215 are provided. The exhaust passage 217 and the reaction chamber 215 Are formed in layers, with the entire structure being provided in the translucent reaction portion 214. Reference numerals 213 and 216 in FIG. 9A are the elastic valve bodies as the elastic block members described above, and can be closed and closed by pressing with the pressing portions 101 and 102 shown in FIG. 9B. It is. The reaction vessel 211 according to the present embodiment corresponds to the fluid circuit because the reaction chamber 215 is provided with two openings.
[0220]
The reaction vessel 211 serves as a rotating body of the liquid introduction device 50 and is capable of sucking and discharging a fluid and covers the lower end portion of the nozzle 22 that can rotate about its axis so as to cover the upper side of the cap 20. Of the nozzle 22 is screwed with the outer surface of the screwing portion 23 of the nozzle 22. Thereby, the nozzle 22 can prevent contact with the reaction vessel 211 to be connected or the liquid stored therein. The outer surface of the cap 20 is threaded, and the reaction vessel 211 is connected to the nozzle 22 by screwing with the inner surface of the opening of the reaction vessel 211. A cylinder (not shown) connected to the nozzle 22 and rotatably provided with the nozzle 22 is provided inside the cylinder-shaped member 21 and rotates to the cylinder-shaped member 21 via a bearing (not shown). Supported as possible. In order to perform suction and discharge of the fluid of the nozzle 22, a rod 24 for moving a plunger (not shown) for adjusting the pressure in the nozzle 22 up and down is provided in the cylinder. At the upper end of the rod 24, an end 24a having a diameter larger than the diameter of the rod 24 is provided. The rod 24 inserted into the rotatable cylinder is provided so that the nozzle 22 or the cylinder cannot rotate.
[0221]
Thus, in the present embodiment, the screwing portion 23 and the cap 20 and the cap 20 and the opening of the reaction vessel 211 are connected by screwing. Yes. Therefore, each screwing needs to be screwed in the tightening direction by the rotation of the nozzle 22 as the rotating body.
[0222]
In the reaction vessel 211 according to the present embodiment, the reaction chamber 215 is provided below the storage chamber 212 and at a position farther from the rotation axis than the storage chamber 212, that is, the axis of the opening. It has been. Accordingly, the liquid dispensed by the dispensing tip by the suction and discharge of the nozzle 22 into the storage chamber 212 is introduced into the reaction chamber 215 by centrifugal force by rotating the nozzle 22 around its axis. Can do. When the liquid was introduced into the reaction chamber 215, the air in the reaction chamber 215 was exhausted into the storage chamber 212 through the exhaust passage 217, and the reaction chamber 215 was filled with the liquid. In this case, the elastic valve bodies 213 and 216 are pressed and sealed. The reaction chamber 215 and the exhaust channel 217 are provided on a frame 214a in which a bottomed groove or recess is formed. As shown in FIG. 9 (b), the opening of the frame 214 a is closed by a transparent thin plate or film 218.
[0223]
As shown in FIG. 9B, the light receiving end portion 78 provided with the pressing portions 101 and 102 for pressing the elastic valve bodies 213 and 216 and the irradiation end portion for irradiating the excitation light for exciting the fluorescent substance are equivalent. The rod lens 75 and the heating element 79 are provided so as to sandwich two large wall surfaces having a large area of the reaction chamber 215. The light receiving end 78 and the rod lens 75 with a heating function are provided so as to be able to contact and separate from the reaction chamber 215 by an opening / closing mechanism 81 shown in FIG.
[0224]
FIG. 10 shows an example of the reaction vessels 131, 141, 151 according to the sixth to eighth embodiments through a cap 20 at the lower end of a nozzle 22 as a rotating body included in the liquid introduction device 50. And the positional relationship with the light receiving end portion 76 of the optical information measuring unit when it is transferred to the reaction measurement position by the liquid introduction device 50. In these cases, the pressing portion may be provided not on the light receiving end portion 76 but on, for example, the rod lens 75 that is the irradiation end portion.
[0225]
FIG. 10A is a front sectional view showing a reaction vessel 131 according to a sixth embodiment. The reaction vessel 131 has an opening and a storage chamber 132 capable of storing a liquid, and the storage chamber 132. A reaction chamber 135 having a regular quadrangular prism shape that is communicated with the chamber 132 and formed thinner than the storage chamber 132, a liquid introduction flow path 133 that communicates between the storage chamber 132 and the reaction chamber 135, and an exhaust flow Path 137. The liquid introduction flow path 133 communicates the side surface of the storage chamber 132 and the upper portion of the reaction chamber 135, and the exhaust flow path 137 includes the lower portion of the reaction chamber 135 and the inner bottom surface of the storage chamber 132. It communicates with. Reference numerals 136 and 138 denote elastic valve bodies that can be closed by pressing.
[0226]
The description of the nozzle 22 as the rotating body of the liquid introduction device 50 is omitted because it is as described with reference to FIG.
[0227]
In the reaction vessel 131 according to the present embodiment, the reaction chamber 135 is below the storage chamber 132 and is more rotationally oriented than the storage chamber 132 than the storage chamber 132, that is, the rotation axis of the nozzle 22 that is a rotating body. 132 is provided at a position far from the axis of the opening. Accordingly, the liquid dispensed by the dispensing tip by the suction and discharge of the nozzle 22 into the storage chamber 132 is introduced into the reaction chamber 135 by centrifugal force by rotating the nozzle 22 around its axis. Can do. Liquid Reaction chamber When introduced into 135, the air in the reaction chamber 135 is exhausted into the storage chamber 132 through the exhaust flow path 137, and when the reaction chamber 135 is filled with liquid, The valve bodies 136 and 138 are pressed and sealed. The reaction chamber 135, the liquid introduction flow path 133, and the exhaust flow path 137 are provided in a frame 134a in which a bottomed groove or depression is formed. The opening of the frame 134a is closed by a membrane.
[0228]
FIG. 10B is a front sectional view showing a reaction vessel 141 according to the seventh embodiment. The reaction vessel 141 has an opening and a storage chamber 142 capable of storing a liquid, and the storage chamber 142. A cylindrical reaction chamber 145 that communicates with the chamber 142 and is thinner than the storage chamber 142, and a liquid introduction channel 143 and an exhaust channel that communicate between the storage chamber 142 and the reaction chamber 145. 147. The liquid introduction flow path 143 communicates the bottom surface of the storage chamber 142 and the slightly upper part of the reaction chamber 145, and the exhaust flow path 147 flows from the slightly lower part of the reaction chamber 145 to the liquid introduction flow path. The path 143 is connected. Reference numerals 146 and 148 denote elastic valve bodies, which can be closed by pressing.
[0229]
Note that the nozzle 22 as the rotating body of the liquid introduction device 50 has been described with reference to FIG.
[0230]
In the reaction vessel 141 according to the present embodiment, the reaction chamber 145 is positioned below the storage chamber 142 and on the axis of rotation, that is, the axis of the opening of the storage chamber 142, rather than the storage chamber 142. It is provided at a far position. Therefore, the liquid dispensed by the dispensing tip by the suction and discharge of the nozzle 22 into the storage chamber 142 is rotated by the centrifugal force around the axis of the nozzle 22 to cause the reaction chamber to rotate. 145 Can be introduced. Liquid Reaction chamber When introduced into the reaction chamber 145, the air in the reaction chamber 145 passes through the exhaust passage 147 and is exhausted into the storage chamber 142. When the reaction chamber 145 is filled with the liquid, it is elastic. The valve bodies 146 and 148 are pressed and sealed. The reaction chamber 145, the liquid introduction flow path 143, and the exhaust flow path 147 are provided in a frame 144a in which a bottomed groove or depression is formed. The opening of the frame 144a is closed by a membrane.
[0231]
FIG. 10C is a front sectional view showing the reaction vessel 151 according to the eighth embodiment. The reaction vessel 151 has an opening and a storage chamber 152 capable of storing a liquid, and the storage chamber 152. The reaction chamber 155 communicates with the chamber 152 and has a regular square column-shaped reaction chamber 155 formed thinner than the storage chamber 152, and a liquid introduction channel 153 that communicates between the storage chamber 152 and the reaction chamber 155. The liquid introduction channel 153 communicates the bottom surface of the storage chamber 152 with the upper portion of the reaction chamber 155. Reference numeral 156 denotes an elastic valve body that can be closed by pressing. The reaction container 151 according to the present embodiment corresponds to the fluid storage portion because the reaction chamber 155 has only one opening. On the other hand, the reaction vessels 131 and 141 correspond to the fluid circuit because each reaction chamber 135 and 145 has two openings.
[0232]
The description of the nozzle 22 as the rotating body of the liquid introduction device 50 is omitted because it is as described with reference to FIG.
[0233]
In the reaction vessel 151 according to the present embodiment, the reaction chamber 155 is located below the storage chamber 152 and more than the storage chamber 152, the rotation axis of the rotating body, that is, the opening of the storage chamber 152. It is provided at a position far from the axis. Therefore, the liquid dispensed by the dispensing tip by the suction and discharge of the nozzle 22 into the storage chamber 152 is introduced into the reaction chamber 155 by centrifugal force by rotating the nozzle 22 around its axis. Can do. Liquid Reaction chamber When introduced into 155, the air in the reaction chamber 155 is exhausted into the storage chamber 152 through the same liquid introduction flow path 153, and when the reaction chamber 155 is filled with liquid, The elastic valve body 156 is pressed and sealed. The reaction chamber 155 and the liquid introduction channel 153 have a frame with a bottomed groove or depression formed therein. 134a Is provided. The opening of the frame 134a is closed by a membrane.
[0234]
Then, based on FIG. 11, the reaction container 221 which concerns on 9th Embodiment is demonstrated.
FIG. 11A is a front cross-sectional view of the reaction vessel 221. The reaction vessel 221 has an opening and a storage chamber 222 capable of storing a liquid, the storage chamber 222 and a flow for introducing a liquid. The reaction chamber 225 communicates via the passage 223 and is formed in a generally square columnar reaction chamber 225 that is formed thinner than the storage chamber 222 as a whole, and the liquid introduction flow that communicates between the storage chamber 222 and the reaction chamber 225. A passage 223 and an exhaust passage 227 are provided. Therefore, the reaction vessel 221 corresponds to the fluid circuit. The liquid introduction flow path 223, the exhaust flow path 227, and the reaction chamber 225 are formed in layers by sandwiching them from the front and back with a transparent thin plate or film 229, and the entirety thereof is provided in the translucent reaction section 224. It has been. Note that reference numerals 228 and 226 in FIG. 11 are, for example, closed positions where the elastic valve bodies as the elastic block members described above are provided, and the gap is closed by pressing with the pressing portion shown in FIG. 9B. And can be closed.
[0235]
The reaction vessel 221 is a rotating body of the liquid introduction device 50, and is capable of sucking and discharging a fluid and covers the lower end of the nozzle 22 rotatable about its axis, A cap 220 made of an elastic body such as rubber is mounted on the nozzle 22 by engaging an inner surface with a protrusion 27 a provided on the outer surface of the mounting portion 27 of the nozzle 22. Thereby, the nozzle 22 can prevent contact with the reaction vessel 221 to be connected or the liquid stored therein. Meanwhile, the reaction vessel 221 is connected to the cap 220 by engaging with the inner surface of the opening of the reaction vessel 221. A cylinder (not shown) connected to the nozzle 22 and rotatably provided with the nozzle 22 is provided inside the cylinder-shaped member 21 and rotates to the cylinder-shaped member 21 via a bearing (not shown). Supported as possible. In order to perform suction and discharge of the fluid of the nozzle 22, a rod 24 for moving a plunger (not shown) for adjusting the pressure in the nozzle 22 up and down is provided in the cylinder. At the upper end of the rod 24, an end 24a having a diameter larger than the diameter of the rod 24 is provided. The rod 24 inserted into the rotatable cylinder is provided so that the nozzle 22 or the cylinder cannot rotate.
[0236]
FIG. 12A shows a partial cross-sectional front view of a state of the reaction vessel 221 to which the cap 220 in a state of being detached from the mounting portion 27 is mounted. FIG. 12B shows a cross-sectional view taken along line AA, FIG. 12C shows a cross-sectional view taken along line BB, and FIG. 12D shows a cross-sectional view taken along CC line. Moreover, FIG.12 (e) shows the side view of the reaction container 221 with which the cap 220 in the state remove | desorbed from the nozzle 22 as shown to Fig.12 (a) was mounted | worn. A protrusion 27 a provided on the mounting portion 27 of the nozzle 22 is inserted into a lateral groove 220 b having a predetermined center angle provided on the cap 220 from a notch 220 c formed slightly larger than the protrusion 27 a provided on the upper end of the cap 220. And engages with the lateral groove 220b so as to be sandwiched. On the other hand, the annular protrusion 220 a provided on the outer surface of the cap 220 is inserted into and fitted into an annular lateral groove provided on the inner wall of the storage chamber 222. A lower outer surface of the cap 220 formed of the elastic body is in close contact with an upper inner surface of the storage chamber 222 of the reaction vessel 211 and closes the opening of the reaction vessel 221. As a result, liquid leakage and gas leakage can be prevented.
[0237]
Thus, in the present embodiment, the mounting portion 27 and the cap 220 are connected by engagement, and the lower outer surface of the cap 220 and the opening of the reaction vessel 221 are connected. Therefore, the reaction vessel 221 is rotated by the rotation of the nozzle 22 as the rotating body.
[0238]
In the reaction vessel 221 according to the present embodiment, the reaction chamber 225 is provided below the storage chamber 222 and at a position farther from the rotation axis than the storage chamber 222, that is, the axis of the opening. It has been. Accordingly, the liquid dispensed into the storage chamber 222 by the dispensing tip by the suction and discharge of the nozzle 22 into the storage chamber 222 is rotated by rotating the nozzle 22 around its axis, thereby causing the reaction by centrifugal force. It can be introduced into the chamber 225. When the liquid was introduced into the reaction chamber 225, the air that was in the reaction chamber 225 was exhausted into the storage chamber 222 through the exhaust passage 227, and the reaction chamber 225 was filled with the liquid. In this case, the elastic valve body is pressed and sealed at the closed positions 226 and 228. The reaction chamber 225, a part of the storage chamber 222, and the exhaust passage 227 are provided in a frame 224a in which holes are formed.
FIG. 13 is a conceptual diagram showing the entire reaction measurement processing system 10 according to the embodiment of the present invention.
[0239]
The reaction measurement processing system 10 performs measurement preparation such as homogenization, extraction, reaction, transfer, thinning, etc., of the suspension contained in the specimen based on the liquid introduction apparatus 50 and various specimens and reagents. A liquid processing region 51 and a reaction measurement region 52 for obtaining optical information for executing real-time PCR on the solution sealed in the reaction chamber of the reaction vessel are provided.
[0240]
As shown in FIG. 13 or FIG. 14, the liquid introduction device 50 has a plurality of (in this example, eight) rotatable nozzles 22 as rotating bodies, and is provided slightly above the tip of the nozzles 22. Various members are connected to the threaded portion 23 to perform various processes such as thinning or thinning of liquid, homogenization of suspension, dispensing of liquid, transfer, removal of impurities, target substance It is a device that enables extraction, stirring, washing, etc. Here, the connection includes mounting, screwing, fitting, fitting, housing, and the like.
[0241]
As shown in FIGS. 13 and 14, the liquid introduction device 50 is covered with a plurality (eight in this example) of nozzles 22 as the rotating body and the cap 20, and is provided with a suction discharge port. A plunger (not shown) is slid in a nozzle 22, a screwing portion 23 provided slightly above the lower end of the nozzle 22 that connects the cap 20 by screwing, and a cylinder 22 a connected to the nozzle 22. And a rod 24 for the purpose. Further, the liquid introduction device 50 rotates each of the eight pulleys 22 and the cylinders 22a concentrically provided to rotate the nozzles 22 and the cylinders 22a about the axis thereof, and each of the eight nozzles 22 and the cylinders 22a. And a motor shaft 83 of the motor 82, eight toothed pulleys 53, and a belt 84 wound around the motor shaft 83. Reference numeral 85 denotes a roller for adjusting the tension of the belt 84. Here, in FIG. 11, the motor 82, the motor shaft 83, the belt 84, and the tension adjusting rotor 85 are omitted for easy viewing. In FIG. 12, the connection of the reaction vessel 11 and the like is omitted.
[0242]
The eight rods 24 are attached so that each of the eight notches provided on the edge of the drive plate 54 is hung with an end 24a projecting in the radial direction with a shape larger than the diameter of the rod 24, The drive plate 54 is connected to a nut portion 87 that is screwed with the ball screw 88. The rod 24 is always urged downward by a spring provided in the cylinder 22a. Therefore, when the rod 24 moves upward, the rod 24 is raised by the nut portion 87. When the rod 24 is lowered downward, the rod 24 is lowered not by the nut portion 87 but by the spring force. The ball screw 88 is rotationally driven by a motor 55 provided on a support member 56 having a U-shaped cross section, whereby the drive plate 54 and the eight rods 24 move up and down all at once.
[0243]
In FIG. 14, reference numeral 23a is a chip removal plate for removing the connected dispensing tips, and the chip removal plate 23a has a support portion 23b extending downward and is screwed with a ball screw 23d. The ball screw 23d is rotationally driven by a motor 23e. Therefore, the chip removal plate 23a can be moved back and forth with respect to the nozzle 22 by the rotation of the motor 23e. The motor 23e, the ball screw 23d, and thus the chip removal plate 23a can be moved up and down by a vertical movement mechanism constituted by a ball screw mechanism provided in the housing 57.
[0244]
An engaging block 47 provided with the cap engaging portions 47a and 47b is screwed into the ball screw 23f. By the rotation of the motor 23g, the cap engaging portions 47a and 47b can approach or separate from the chip removal plate 23a.
Reference numeral 23c denotes a pressure sensor connection flow path.
[0245]
The support member 56 can be moved up and down independently of the chip removal plate 23 a by a vertical movement mechanism constituted by a ball screw mechanism provided in the housing 57. The motor 58 rotates the ball screw. Below the housing 57, a magnet 89 is moved in the left-right direction in the figure, and a motor 59 for moving the magnet 89 for applying or removing a magnetic field from the outside of the dispensing tip connected to the nozzle 22 in the tip. , A magnetic means including a horizontal bar 60, a rod 61, and a magnet 89 is provided.
[0246]
The liquid introduction device 50 is provided so as to be suspended from the upper side, and moves along the X axis and the Y axis using a linear motion mechanism (not shown) so as to cover the entire region of the reaction measurement processing system 10 and other necessary regions. It is provided so as to be movable by a mechanism.
[0247]
The liquid processing region 51 of FIG. 13 includes a cartridge container 62 having eight specimen storage wells 62a for storing a suspension in which the specimen is suspended, a matrix container 65 having 5 columns × 8 rows of wells, and a real time It has eight cartridge containers 70 for storing various reagents, substances or processing results necessary for executing PCR, and a holding rack 70a for holding the eight reaction containers 11 and caps 20.
[0248]
Further, each of the specimen containing wells 62a is provided with a barcode 62b indicating information relating to the specimen. The bar code 62b is read by moving so that the bar code reader 63 that reads the bar code scans. Reference numeral 64 represents a moving mechanism of the bar code reader 63.
[0249] In the matrix-like container 65, a filter-incorporated chip row 66 and a dispensing tip row 67 for homogenizing the suspension containing the specimen and then removing contaminants by sucking and discharging the liquid. A row of containers 161 in which filter-containing containers 161 (or column connection containers 171) for homogenizing the suspension containing the specimen by rotation and removing contaminants are arranged, and reagents necessary for PCR Well 69 rows are held.
[0250] FIG. 15A shows a usage state when the filter-incorporated chip 66 held in the matrix container 65 in the processing area is connected to the liquid introducing device 50 and used.
[0251] The filter built-in chip 66 is used by being fitted to the dispensing chip 67. The dispensing tip 67 is provided with a flange 67a provided at the upper end, a storage portion 67b that stores liquid, and a fitting portion that is provided below the storage portion 67b and that fits into the opening of the filter built-in tip 66. It has a portion 67c and a small-diameter portion 67d that communicates with the storage portion 67b below the storage portion 67b, has a smaller diameter than the storage portion 67b, and has a liquid suction / discharge port.
[0252] The filter built-in tip 66 has a flange 66a provided at the upper end and an opening that can be fitted by the fitting portion 67c of the dispensing tip 67, and can store a liquid. The storage part 66b in which 100 is built in, and the small-diameter part 66c which is provided below the storage part 66b, communicates with the storage part 66b, and has a smaller diameter than the storage part 66b. The filter 100 needs to have a pore diameter corresponding to an object to be filtered.
[0253] In order to remove contaminants from the suspension or to separate the target using the filter built-in chip 66, the nozzle 22 provided in the liquid introducing device 50 as shown in FIG. And the engagement member 99 provided in the liquid introduction device 50 and the flange 67a provided at the upper end of the dispensing tip 67 are engaged with each other. Connecting. Next, the filter built-in chip 66 is connected by fitting the opening of the storage part 66 b of the filter built-in chip 66 into the fitting part 67 c of the dispensing chip 67. In such a coupled state, the liquid is sucked or discharged so that the liquid passes through the filter 100, thereby separating impurities and target substances in the liquid.
[0254] Further, instead of connecting the filter built-in chip 66, as shown in FIG. 15B or FIG. 15C, the filter built-in container 161 held in the matrix-shaped container 65 in the liquid processing region 51. Alternatively, the column connection container 171 may be used to separate impurities and target substances in the liquid by using the rotation of the liquid introduction device 50. The filter built-in container 161 has an opening to which the lower end portion of the nozzle 22 can be connected, and is partitioned by a cylindrical storage chamber 162 capable of storing a liquid and a filter 100 having a predetermined pore diameter. The filter chamber 164 extends obliquely downward from the chamber 162, and the storage chamber 166 communicates with the filter chamber 164 and is detachably attached to the filter chamber 164. Reference numeral 163 denotes a flange used for removal by the chip removal plate 23a.
[0255]
In the filter built-in container 161, the axis of the opening to which the lower end of the nozzle 22 can be connected becomes the rotation axis. The filter chamber 165 is located farther from the axis than the storage chamber 162, and the storage chamber 166 is located farther from the axis than the filter chamber 165. Therefore, the rotation of the nozzle 22 causes the filter built-in container 161 connected to the nozzle 22 to rotate, so that the liquid stored in the storage chamber 162 passes through the filter chamber 164 and rotates into the storage chamber 166. To reach. In the filter built-in container 161, a line connecting the storage chamber 162, the depression 163, the filter chamber 164, and the storage chamber 166 forms a substantially acute angle with the axis.
[0256]
FIG. 15C shows the column connection container 171. The column connection container 171 has an opening to which the lower end of the nozzle 22 can be connected. The column connection container 171 communicates with a cylindrical storage chamber 172 capable of storing liquid and the storage chamber 172 and has a predetermined adsorptivity. It has a column 174 in which a solid 175 is stored, and a storage chamber 176 that communicates with the column 174 and is detachably attached to the column 174. Reference numeral 173 denotes a flange used for removal by the chip removal plate 23a.
[0257]
In the present column connection container 171, the axis of the opening to which the lower end of the nozzle 22 can be connected becomes the rotation axis. The column 174 is provided to extend obliquely downward with respect to the storage chamber 172 so as to form an acute angle downward with respect to the rotation axis. The column 174 is formed from the storage chamber 172. Is also provided at a position far from the rotational axis. Therefore, the column connection container 171 connected to the lower end portion of the nozzle 22 is rotated by the rotation of the nozzle 22 as a rotating body, so that the liquid stored in the storage chamber 172 is once depressed. 173, is introduced into the column 174 through the recess 173, and eventually reaches the storage chamber 176.
[0258]
In FIG. 15 (b) or (c), a small amount of liquid can be obtained by providing a depression in the bottom of the storage chambers 162 and 172 and communicating with the filter chamber 164 or the column 174 through the depression. Even so, the liquid can be efficiently transferred to the column 174 by once storing the liquid in the recess.
[0259]
Returning to FIG. 13, the reaction measurement region 52 is sealed by introducing a target container into the reaction chamber 15 (or 33, 41a, 115, 135, 145, 155, 215, 225). The static PCR unit 80 that holds the reaction vessels 11 (31, 41, 111, 131, 141, 151, 211, 221) so that temperature control and optical measurement are possible, or temperature control and optical measurement are possible. The dynamic PCR unit 90 is inserted so as to be movable up and down. The static PCR unit 80 and the dynamic PCR unit 90 are used by switching with a switch. The static PCR unit 80 receives light by sandwiching each reaction chamber 15 from both sides along its thickness direction in order to heat or cool the reaction chamber 15 of the reaction vessel 11 held in a stationary state. A rod lens 75 around which an end 78 and a linear heating element 79 are wound is provided. The light receiving end 78 and the rod lens 75 are provided so as to be close to and away from the reaction chamber 15. The rod lens 75 irradiates each reaction chamber 15 with excitation light at each irradiation position in order to obtain optical information from the labeling substance when a fluorescent substance is used as the labeling substance in the reaction chamber 15. This corresponds to the irradiation end of the optical information measuring unit. In addition, a trigger light source 71 that supplies excitation light to the rod lens 75 at each irradiation end via the optical fiber 74 and light from the reaction chamber 15 are received by the light receiving end 78 and received via the optical fiber 77. And a photomultiplier tube 73 for converting the converted light into an electrical signal.
[0260]
On the other hand, as shown in FIG. 13 or FIG. 21, the dynamic PCR unit 90 includes two movable walls 90a and 90b provided so as to sandwich the reaction chamber 15 of the reaction vessel 11 from both sides along its thickness direction. And regions 91, 92, 93 provided on the movable walls 90 a, 90 b and provided with heating ends or cooling ends for heating or cooling the reaction chamber 15 for each reaction vessel 11. They are arranged in the vertical direction. In addition, a region 94 where a light receiving end for measuring optical information is located is provided for each reaction vessel 11 at the bottom of the row along these regions 91, 92, 93. Outside the movable walls 90a and 90b, a light receiving end 78 is positioned in each of the regions 91 to 93, and the rod lens 75 for irradiating excitation light is positioned in the region 94 and the movable wall 90a. , 90b are provided so as to be close to and away from the reaction chamber 15. The region 94 is formed transparently, and the PCR units 80 and 90 are provided with a blower 80 c that blows air in a direction along the arrangement of the reaction vessels 11. In addition, the cooling air injection part is provided in the space between the regions 91, 92, and 93 where the heating end or cooling end shown in FIG. 21 is provided, and the temperature set between the regions decreases. In this case, the temperature transition can be performed smoothly. The light receiving end 78 and the rod lens 75 (79) of the static PCR unit 80 and the movable walls 90a and 90b of the dynamic PCR unit 90 are opened and closed by an opening and closing mechanism 81.
[0261]
In the dynamic PCR unit 90, control of temperature control and measurement of optical information can be replaced with movement between the regions, so that control and processing are simplified. In addition, the temperature can be changed instantaneously by moving to a different temperature range, compared to the case where the temperature of the heating element or cooling body having a large heat capacity is raised or lowered. Fine and precise temperature control can be performed. Therefore, it can be used for processing that requires accuracy.
[0262]
The reaction vessel 11 is further connected to the nozzle 22 with its opening 13 covered with the cap 20, and is connected to the nozzle 22 as shown in FIG. 1 (b), FIG. 7 (c) to (e), FIG. 9 or FIG. As shown in FIG. 2, the PCR unit 80 is inserted into each of the eight holes 80a, supported by the stepped portion of the flange 12a of the opening 13, and the reaction unit 14 is inserted into the slit 80b of the PCR unit 80. Below the PCR unit 80, along the thickness direction of the reaction portion 14, one light wall side, that is, the wall surface side where the film 18 is provided is provided with the light receiving end portion 78, and on the other wall surface side. A rod lens 75 around which the heating element 79 is wound is provided.
[0263]
The light receiving end portion 78 and the rod lens 75 are provided so as to be able to contact and separate from the reaction portion 14 simultaneously or individually by an opening / closing mechanism 81. The light-receiving end portion 78 on the side surface of the reaction portion 14 on which the membrane 18 is provided has the membrane 18 and the elastic portion at locations corresponding to the positions of the elastic valve body 16a and the hole portion 17b that are the closed positions. Pressing portions 101 and 102 for pressing and deforming the valve body 16a are provided so as to protrude in the normal direction of the side surface of the flat light receiving end portion 78 at the tip of the fiber bundle. The heating / cooling section has a blower 80c as a cooling end. The blower 80c can blow air along the direction in which the eight reaction vessels 11 are arranged. For example, when the rod lens 75 around which the heating element 79 is wound is separated from the reaction vessel, the heat can be efficiently controlled by sending in air for the heat radiation of the reaction chamber 15. When installing the reaction vessel 11 in the PCR unit 80, the open / close mechanism 81 moves the light receiving end 78 and the rod lens 75 to a position away from the reaction unit 14 to perform heating and cooling. The light receiving end portion 78 and the rod lens 75 are brought close to or in contact with the reaction portion 14. Regarding the temperature control for the light receiving end 78 and the heating element 79, the magnitude of the current to the light receiving end 78, the heating element 79, the reaction chamber of the rod lens 75 is controlled by a program control from an information processing device (not shown). 15 is set by setting the distance to 15 or the timing and intensity of blowing by the blower 80c.
[0264]
The reaction measurement region 52 is provided with an optical information measuring unit for measuring optical information in the reaction chamber 15. Here, assuming that the fluorescent substance is labeled with various fluorescent substances in order to measure the amount of the target substance in the reaction chamber 15, the optical information measuring unit has eight units as shown in FIG. In order to irradiate the reaction part 14, a rod lens 75 as an irradiation end and a trigger light source 71 for irradiating excitation light are shown in FIG. 1 (c). A light receiving end 78 for receiving light emission at a predetermined light receiving position for each of the eight reaction portions 14, that is, a large wall surface having the largest inner area of the wall portion surrounding the reaction chamber 15, and each light receiving end portion. A light receiving portion 72 having a photomultiplier tube 73 for converting the light received at 78 into an electric signal is provided. Similarly to FIG. 1 (c), also in FIG. 9 (a) or FIG. 10, the rod lens 75 around which the heating element 79 as the irradiation end is wound is provided on the wall portion having the largest area. The light receiving end portion 76 is provided on the wall surface having the smallest area. However, the configuration can be simplified by providing the rod lens 75 as the irradiation end and the light receiving end 76 on the same wall surface. Or it can also provide in the wall surface which the rod lens 75 and the light-receiving end part 76 which are irradiation ends face each other.
[0265]
FIG. 16 shows a specific example of the trigger light source 71, the trigger light source 71, and the light receiving unit 72. The trigger light source 71 includes a rotating plate 103 that supports a bundle of optical fibers 74 extending to each irradiation end of each of the eight reaction portions 14, and a hole formed at a position corresponding to the bundle of optical fibers 74. And an optical fiber 107 for guiding laser light from each laser light source (not shown) that emits laser light having a plurality of types (in this example, four types) of wavelengths. The support plate 106 is rotatably supported by a support plate 106 arranged at equal intervals on a circumference along the travel path of the optical lens 105, and the rotating plate 103 and the rotating plate 104 connected to each other. Is provided with a shaft 108 which is supported so as not to rotate. According to the trigger light source 71, light from four types of light sources that generate laser beams having a plurality of types of wavelengths is switched over time, and all the eight reaction chambers 15 are simultaneously transmitted at the irradiation end. Can be irradiated with light. The trigger light source 71 has the light source selection unit. The rod lens 75 is provided at the tip of the optical fiber 74.
[0266]
The light receiving unit 72 includes a support plate 109 that supports eight optical fibers 77 extending to the respective light receiving end portions 78 of the eight reaction chambers 15 so as to be arranged at predetermined intervals, and the support plates 109. On the circumference corresponding to the arrangement position of the optical fibers 77, a rotating plate 110 having a hole 111 having an area corresponding to the diameter of the optical fiber 77 is provided, and the rotating plate 110 can be rotated independently of the rotating plate 110. The rotating plate 112 on which a plurality of types (four types in this example) of optical filters 113 are arranged and the support plate 109 are supported so as not to rotate, and the rotating plate 110 and the rotating plate 112 are supported so as to be independently rotatable. Shaft 114. The light receiving unit 72 corresponds to a light receiving position selection unit and an optical filter selection unit. The selection of the optical fiber 77 from the light receiving end portion 78 corresponds to the light receiving position selecting portion.
[0267]
According to the optical information measurement unit according to the present embodiment, the trigger light source 71 rotates four predetermined light sources for a certain period of time by rotating the rotation plate 103 and the rotation plate 104 by a predetermined angle. By rotating intermittently every other one of the reaction chambers 15 of each of the eight reaction vessels is irradiated at once. Then, the fluorescence excited in the reaction chamber 15 of each reaction vessel 11 is guided from the light receiving end portion 76 to the light receiving portion 72 through the optical fiber 77 to the narrow wall portion of each reaction chamber 15. Then, the rotating plate 110 intermittently rotates the rotating plate 110 once in the duration of the fluorescence while the one type of excitation light is irradiated, thereby sequentially turning each of the eight reaction vessels 11. While the light from the reaction chamber is guided to the rotating plate 112 and further receiving the fluorescence from one reaction vessel 11, the rotating plate 112 is rotated once to pass through the four types of optical filters 113 sequentially. Then, light is introduced into the PMT 73. This operation is sequentially performed for four types of excitation light.
[0268]
FIG. 17 shows a trigger light source 115 and a light receiving unit 116 according to another embodiment.
The trigger light source 115 includes a support plate 117 that supports eight optical fibers 74 extending to rod lenses 75 serving as irradiation end portions of the eight reaction units 14 so as to be arranged at predetermined intervals, and the support plate 117. A rotating plate 118 having a hole 119 having an area corresponding to the diameter of the optical fiber 74 on the circumference corresponding to the arrangement position of each of the optical fibers 74, and rotatable independently of the rotating plate 118 And a support plate 120 in which optical fibers 121 from a plurality of types (four types in this example) of light sources are arranged at predetermined intervals, the support plate 117 is not rotatable, and the rotary plate 118 is rotatable. It has a shaft 122 that supports it. The trigger light source 115 has the light source irradiation position selection unit.
[0269]
The light receiving unit 116 includes a support plate 123 that supports a bundle of eight optical fibers 77 extending from the light receiving end portions 76 of the eight reaction chambers 15, and the optical fibers 77 of the support plate 123. A plurality of (four in this example) holes having positions and sizes corresponding to the bundles are drilled, and a shaft 126 that rotatably supports the four types of optical filters 125 is provided. Therefore, the light receiving unit 116 has the optical filter selection unit.
[0270]
According to the optical information measuring unit according to the present embodiment, excitation light for fluorescence emission from four types of light sources is provided on the rotating plate 118 by intermittently rotating the rotating plate 118 once. Excitation light is guided through the optical fiber 74 to the reaction chambers 15 of the eight reaction vessels 11 through the holes 119. Then, the fluorescence excited in each reaction chamber 15 irradiated with the excitation light is guided to the light receiving unit 116 via the optical fiber 77. During the time when the fluorescence from one reaction chamber 15 lasts, the rotating plate 124 is sequentially rotated to sequentially pass the four types of optical filters 125 and introduce them into the photomultiplier tube 73.
[0271]
FIG. 18 shows an example of a rod lens as the irradiation end.
[0272]
Returning to FIG. 13 again, the reaction measurement region 52 further accommodates the reaction vessel 11 to accommodate and rotate the reaction vessel 11 and the eight-unit container accommodation portion 204 corresponding to the rotating body. The liquid introduction unit 200 is provided. The liquid introduction part 200 accommodates the casing 201 in which the eight series of container accommodating parts 204 are accommodated and the reaction container 11 to be rotated, which is drilled in the upper part of the casing 201, in the container accommodating part. And a slit portion 203 for easily accommodating a protruding portion such as the reaction portion 14 of the reaction vessel 11.
[0273]
FIG. 19A is a plan view of the eight container housing portions 204 provided in the casing 201. The container housing portion 204 is provided with a concave portion 205 and is a portion into which the reaction portion 14 of the reaction container 11 to be housed is inserted.
[0274]
FIG. 19B is a front sectional view of the container housing portion 204 that houses the reaction container 11 conceptually represented. FIG. 19C shows a cross-sectional side view of the casing 201 of the liquid introduction part 200 and the container housing part 204 provided therein.
[0275]
The container accommodating portion 204 is rotated in a state where the reaction container 11 is accommodated. The rotation axis of the container accommodating portion 204 is provided so as to penetrate the accommodated container. According to the present embodiment, since the liquid introduction unit 200 is provided in addition to the liquid introduction device 50, the processing can be performed efficiently.
[0276]
FIG. 20 shows an example of a reaction vessel 191 according to a tenth embodiment for thinning the liquid instead of thinning the liquid. The reaction container 191 has a storage chamber 192 having an opening and capable of storing a liquid, and a reaction chamber 193 formed narrower than the storage chamber 192. The opening of the reaction container 191 The liquid can be introduced into the reaction chamber 193 by being connected to the nozzle 22 as a liquid introduction portion provided in the nozzle 22. Here, reference numeral 194 denotes a flange that can be attached and detached by the chip removal plate 23a, and reference numeral 195 denotes a flow path.
[0277]
FIG. 21 shows the dynamic PCR unit 90 and the reaction vessel 221 that receives processing in the PCR unit 90.
[0278]
As described above, the PCR unit 90 includes two movable walls 90a and 90b formed of a heat insulator so as to sandwich the eight movement paths through which the eight reaction vessels 221 move from both sides. Yes. The vertical movement of the reaction vessel 221 is driven while being mounted on the nozzle 22 by the motor 58 described above. The moving path direction is a vertical direction. As shown in FIG. 13, the PCR unit 90 has eight groups of regions arranged in the horizontal direction. One region group includes four vertical directions as shown in FIG. Have regions 91, 92, 93, 94 arranged in an array. Each of the regions 91, 92, 93, 94 is arranged at a position through which a thin layer of the reaction chamber 225 passes in the reaction vessel 221, and the cylindrical portion including the nozzle 22 of the reaction vessel 221 is adjacent to the region 91. It is formed so as to pass through the interval between the region groups.
[0279]
Further, the region 94 is formed transparent, and a region 94 provided on one of the movable walls 90a is provided with a fiber tip 95 corresponding to a light irradiation end portion by irradiating light from the trigger light source 71, The region 94 provided on the other movable wall 90 b is provided with a light receiving end portion 78. At that time, the optical axis of the fiber tip 95 and the optical axis of the light receiving end 78 are provided so as to be inclined by a predetermined angle. Alternatively, fiber rod glass 95a, 78a is provided on one or both of the irradiation end portion and the light receiving end portion, and the light irradiation direction and the light receiving direction are shifted by a predetermined angle, thereby irradiating the light receiving end portion. The influence of light from the end can be reduced.
[0280]
In addition, each of the regions 91 to 93 corresponds to the temperature control in the PCR process, for example, the region 91 is provided with a heating end portion that is kept at a constant temperature of 94 ° C., and the region 92 is, for example, from 50 ° C. A heating end capable of raising and lowering the temperature in the range of 60 ° C. is provided, and the temperature is set according to the processing content. Further, the region 93 is provided with a heating end portion that is brought to a constant temperature state of 72 ° C. The time for the reaction chamber 225 to pass through one cycle from each region 91 to region 94 is, for example, about 15 seconds, and the movement is repeated a plurality of times.
[0281]
Next, the flow of processing using the reaction measurement processing system 10 described above will be described based on FIG. 13 and FIG. 22 conceptually showing the flow of processing.
[0282]
Here, a case where measurement is performed using a real-time PCR method in order to measure the amount of DNA contained in a predetermined specimen will be described. Real-time PCR is a method for measuring the concentration of nucleic acid using a nucleic acid probe. For example, when a nucleic acid probe labeled with a fluorescent dye is hybridized to the target nucleic acid, the fluorescent dye emits light to the extent that it depends on the type and base sequence of the base to which the fluorescent dye is bound. A reagent that emits fluorescence by utilizing the phenomenon of decreasing or the intensity of luminescence increasing by removing the nucleic acid probe from the target nucleic acid (luminescence quenching phenomenon) or being inserted into double-stranded DNA In addition to the reaction system, a method (intercalator method) is used that uses a method of detecting fluorescence accompanying amplification and detects the fluorescence intensity.
[0283]
The cartridge container 62 of the reaction measurement processing system 10 contains a specimen made of a suspension in which biological tissue such as skin obtained from eight patients or the like is suspended in advance. The well 69 and the cartridge container 70 contain, for example, reagents necessary for PCR, DNA polymerase, reaction buffer solution, fluorescent reagent, primer, and other reagents in advance. The nozzles 22 of the liquid introduction device 50 are connected together by fitting them together by pushing down the nozzles 22 with respect to the eight dispensing tips held in the tip rack (not shown) by a lifting mechanism (not shown). Then, by repeating the suction and discharge of the specimens stored in the cartridge container 62 all at once, the living tissue that is a solid substance contained in the suspension is crushed or homogenized to the cell level. Next, the liquid introducing device 50 is moved to suck the suspension into the dispensing tip, and the position where the eight filter built-in containers 161 are accommodated, that is, the matrix container 65. To the position of the third row from the left in the figure, and the suspension contained in the dispensing tip is discharged into each of the storage chambers 162 of the eight filter built-in containers 161.
[0284]
The lower end of the nozzle 22 is inserted into and connected to the opening of the storage chamber 162. In this state, the filter built-in container 161 is lifted up above the matrix-shaped container 65, and the eight nozzles 22 are rotated at the same time to rotate the filter built-in containers 161 together with the nozzles 22. Then, the homogenized suspension accommodated in the storage chamber 162 of the filter built-in container 161 passes from the storage chamber 162 through the filter 100 in the filter chamber 164 by centrifugal force due to rotation. It moves to the storage chamber 166. The filter 100 captures the contaminants, and a solution containing the target DNA free of contaminants is obtained in the storage chamber 166. The storage chamber 166 is removed from the filter chamber 164 of the filter built-in container 161, a dispensing tip is connected, the solution is sucked, and necessary reagents such as a probe labeled with a fluorescent substance are stored. The solution is transferred to a predetermined well 69 of the cartridge container 70 and discharged to produce a solution mixed with a necessary reagent.
[0285]
Next, the nozzle head of the liquid introduction device 50 is moved to move the eight nozzles 22 to a chip rack (not shown), and the lifting mechanism of the nozzle 22 is operated to be held by the chip rack. The nozzles 22 are inserted into eight unused dispensing tips 127 and connected. Next, the dispensing tip 127 is moved to the eight wells 69, and the solutions 128 accommodated in the wells 69 are sucked into the unused eight dispensing tips 127 all at once. . Then, as conceptually shown in FIG. 22 (a), it is transferred to the eight reaction vessels 11 held in the holding rack 70a, and the solution 128 is discharged into the respective storage chambers 12 thereof. . After the discharge, the eight dispensing tips 127 are removed from the nozzle 22 of the liquid introducing device 50 by the tip removing plate 23a and discarded.
[0286]
Next, the liquid introduction apparatus 50 moves to the position of the holding rack 70a in which the eight caps 20 are accommodated, and inserts the nozzles 22 into the eight caps 20 all at once. By rotating 22, the eight caps 20 are connected at the respective screwing portions 23.
[0287]
Next, as shown in FIG. 22 (b), the nozzle head of the liquid introduction device 50 is moved to a position where the reaction vessel 11 of the holding rack 70 a is held and connected to the nozzle 22. The cap 20 is inserted into the opening 13 and the storage chamber 12 of each reaction container 11 in which the solution 128 is accommodated, and the reaction container 11 is screwed into the cap 20 by rotating the nozzle 22 all at once. Connect with. Next, after pulling up the reaction vessel 11 above the holding rack 70a, the nozzle 22 in the same rotation direction as the rotation for screwing at the cap 20 and the opening 13 and therefore the nozzle 22 The reaction vessels 11 connected to are simultaneously rotated at a high speed. In the state where the reaction vessel 11 is housed in the holding rack 70a, the reaction chamber 15 is held in a state of being inserted into slit-like spaces provided in the holding rack 70a. During the rotation of the nozzle 22, the reaction vessel 11 does not rotate.
[0288]
Then, as shown in FIG. 22C, the solution 128 accommodated in each of the storage chambers 12 moves to the reaction chamber 15 by centrifugal force and is introduced into the reaction chamber 15.
[0289]
The reaction vessel 11 into which the solution has been introduced into the reaction chamber 15 is transferred to the PCR unit 80 by the liquid introduction device 50 with the cap 20 in place, and the holes 80a and slits 80b of the PCR unit 80 are Hold to be supported by the part.
[0290]
As shown in FIGS. 22D and 22E, the light receiving end 78 is brought close to the reaction chamber 15 by the opening / closing mechanism 81, and the pressing portions 101, 102 are moved to the corresponding closed positions 25, 26, respectively. Is pressed to deform the closed position, that is, the elastic valve body 16a and the membrane 18, and the inside of the reaction chamber 15 is sealed at the same time.
[0291]
Next, not only the light receiving end portion 78 but also the rod lens 75 around which the heating element 79 corresponding to the heating / cooling end portion is wound is moved from the back side of the reaction portion 14 by the opening / closing mechanism 81 to the reaction chamber 15. The temperature is controlled based on the PCR method by bringing them close to or in contact with each other. At this time, in the present embodiment, the rod lens 75 around which the heating element 79 is wound is brought into direct contact with or in contact with each reaction chamber 15, so that it has faithful response to temperature changes. A container for PCR can be provided.
[0292]
During the PCR amplification process, for example, as shown in FIG. 16, excitation light for exciting a fluorescent substance, which is a labeling substance used in each reaction chamber 15, is emitted from the trigger light source 71 to the rotating plate 104. The light from the light source of the selected wavelength is irradiated into the reaction chambers 15 simultaneously through the optical fiber 74 and at the rod lens 75 which is each irradiation end. At that time, the light receiving unit 72 irradiates the eight reaction chambers 15 all at once. At that time, the light receiving unit 72 sequentially selects light emitted from the light receiving end portions 76 at the respective light receiving positions for the eight reaction chambers 15 by the rotating plate 110, and in the intermittent rotation of the rotating plate 110. The light input to the PMT 73 when the corresponding optical filter 113 is selected by rotating the rotating plate 112 intermittently and sequentially within a time for selecting light reception from one light receiving end 76. Get the data. The above operation is measured by changing the light received from all the reaction chambers 15 into electric signals for all four types of light wavelengths. Thereby, the state of the emission intensity of the fluorescent substance can be measured in real time, and the amount of DNA to be the target can be measured.
[0293]
Further, when the rod lens 75 around which the heating element 79 is wound is separated from the reaction chamber 15 and the reaction chamber 15 is cooled, the rod lens 75 is separated from the reaction chamber 15 and is simultaneously sent by the blower 80c. Then, each reaction vessel 11 can be efficiently dissipated from the reaction chamber 15 by being exposed to cold air.
[0294]
According to the present embodiment, a suspension containing a specimen is homogenized, a solution containing the target DNA is extracted from the homogenized suspension, and a solution obtained by mixing various reagents with the DNA is thinned. The operation until obtaining optical information can be performed efficiently and consistently with a compact device while performing accurate and highly responsive temperature control on the thinned solution.
[0295]
In the above description, as the liquid introduction unit, the liquid introduction device 50 is configured to introduce the liquid stored in the storage chamber into the reaction chamber by connecting a reaction vessel to the nozzle 22 as a rotating body. Without being limited thereto, the reaction vessel 11 is connected to the nozzle of the liquid introduction device 50 in the container housing portion 204 of the liquid introduction portion 200 as a liquid introduction portion, and the reaction vessel 11 is introduced into the liquid introduction portion. You may make it carry out by accommodating in each container accommodating part 204 of the part 200, and rotating. In particular, when the solution to be stored in the reaction vessel 11 is generated, the movement of the liquid introduction device 50 is simplified by using the liquid introduction unit 200.
[0296]
As the reaction vessel, the chip-like reaction vessel 41 is connected to the nozzle 22 of the liquid introduction device 50 via the cap 42, so that the reaction chamber is not used as a rotating body but using the suction / discharge function of the nozzle 22. A liquid may be introduced into the gap 41a.
[0297]
In this case, the liquid introduced into the gap 41a moves the cap engaging portions 47a and 47b slightly upward with respect to the chip removal plate 23a after reacting with the gap 41a sealed. The nozzle 42 and the gap 41a are made to communicate with each other by opening the hole portion 42f, and the sealed state is released, and the nozzle 22 is discharged through the small-diameter portion 46 for production. Things can be recovered.
[0298]
The above embodiment has been specifically described for better understanding of the present invention, and does not limit other embodiments. Therefore, changes can be made without changing the gist of the invention. For example, the Optical information measurement unit As described above, the light may be distributed using an optical system such as a half mirror, a mirror, or an optical filter, instead of selecting the light by switching in time as described above.
[0299]
Further, the various mechanisms are not limited to those described above. For example, a gear mechanism can be used as the nozzle rotation mechanism instead of the belt mechanism. Further, for example, it is possible to use the rotation mechanism disclosed in PCT / JP02 / 01147 (WO02 / 063300 A1) made by the present inventor.
[0300]
The shape of the reaction vessel is not limited to that described above, and the storage chamber portion may not be cylindrical, but may be prismatic or spherical. Further, the example in which the cap is interposed and connected to the nozzle has been described. However, the cap may be directly connected to the nozzle without interposing the cap. The nozzle rotation mechanism, the suction / discharge mechanism, the number of nozzles and the number of various containers of the liquid introduction device 50 are not limited to the above description. The number of nozzles and containers may be one or a number other than eight. Moreover, although the said filter was used in order to remove the contaminant in suspension, you may use it in order to capture | acquire the target substance.
The rotation support shaft may be provided not only along the axis of the opening 13 of the storage chamber 12 as shown in FIG. 5 but also in parallel with the axis of the opening 13. Since this rotation support shaft is a part of the container, the rotation around the rotation support shaft of the container in this case also corresponds to the rotation of the container.
[0301]
In the above description, the optical information measuring unit in FIG. 16 has been described. However, the optical information measuring unit in FIG. 17 may be used. Further, although the heating / cooling section is provided on both sides of the reaction chamber, it may be provided only on one side. Further, the heating / cooling unit may use liquid or gas instead of solid. Furthermore, in the above description, an example mainly relating to thinning of the liquid has been given, but it is also possible to make the liquid thin.
Furthermore, in the above description, in FIG. 13, both the static PCR unit and the dynamic PCR unit are provided and switched to use, but only one of the PCR units may be provided.
[0302]
In addition, each of the above reaction containers, storage chambers, reaction chambers, flow paths, reaction sections, rotating body support shafts, dispensing tips, light measurement sections, caps, various containers, reagents, nozzles, heating / cooling sections, etc., liquids The introduction part and various mechanisms can be arbitrarily combined while being appropriately deformed.
[Industrial applicability]
[0303]
The present invention relates to a reaction vessel, a reaction measurement device, and a liquid rotation processing device according to the present invention. The present invention is, for example, fields that require processing, testing, and analysis mainly related to genes such as DNA, RNA, mRNA, rRNA, tRNA, and plasmids, for example, industrial fields, agricultural fields such as food, agricultural products, and marine products processing, It is related to all fields such as medicine field, hygiene, health care, disease, genetic field, etc., biochemistry or biology field, etc. In particular, the present invention can be used for analysis and inspection handling various DNAs such as PCR and real-time PCR.
[Explanation of symbols]
[0304]
10 Reaction measurement processing system
11, 11a, 31, 41, 131, 141, 151, 191, 211, 221 reaction vessel
12, 32, 66, 132, 142, 152, 212, 222 Reservoir
14, 14d, 134, 144, 154, 214, 224 reaction section
15,135,145,155,215,225 reaction chamber
18 Membrane
20 cap
22 Nozzle (rotating body)
16, 133, 143, 153, 212, 223 Liquid introduction flow path
17, 137, 147, 217, 227 Exhaust flow path
16a Elastic valve body (closed position)
17b Hole (closed position)
138,136,148,146,156,213,216,226,228 closed position
41a Gap (reaction chamber)
50 Liquid introduction device
51 Liquid processing area
52 Reaction measurement area
71 Trigger light source
72 Receiver
73 PMT (photomultiplier tube)
75 Rod lens (irradiation end)
76,78 Light receiving end
79 Heating element (heating / cooling part)
200 Liquid introduction part

Claims (45)

A storage chamber having an opening and capable of storing liquid;
A reaction chamber formed thinner or thinner than the storage chamber, at least a part of which is translucent or semi-translucent,
A container having at least one flow path communicating between the storage chamber or the outside and the reaction chamber, the container being formed so as to be connectable to a rotatable rotating body as a liquid introducing portion provided outside. The liquid can be introduced into the reaction chamber by connecting to the liquid introducing portion, and when connected, the rotation axis of the rotating body passes through the opening of the container and the reaction chamber is A reaction vessel which is formed so as to be located farther from the rotation axis than the storage chamber and is rotatable together with the rotating body. The reaction container according to claim 1, wherein the opening has a cap that can be detachably connected to the opening. Said flow path and the reaction chamber, a flat frame having a groove or hole, the frame according to claim 1 or formed from a film from one side or soft material covering the both surfaces of claim 2 The reaction container in any one. The rotating member is a rotatable nozzle can suction and discharge of gas, the nozzle reactor according to any one of claims 1 to claim 3 having an axis of rotation along its axial direction. The flow path includes a liquid introduction flow path for introducing liquid from the storage chamber into the reaction chamber, and an exhaust flow path for exhausting gas from the reaction chamber, and the liquid introduction section rotates. The reaction vessel is connectable to the rotating body, and when connected, the reaction chamber is positioned farther from the rotation axis of the rotating body than the storage chamber. it is formed, and the reaction vessel according to any one of claims 3 to claims 1 is rotatable together with the rotary member. The reaction container according to claim 5 , wherein a deformable soft member is provided in at least a part of the flow path or the reaction chamber, and the reaction chamber can be sealed by deforming the soft member. The reaction container according to claim 6, wherein the soft member is an elastic block member that can be deformed by pressing, and has a gap through which liquid and gas can pass. Wherein the reaction vessel when connected to said rotating body, the reaction vessel according to claim 5 of stone claim 7 having a rotating support shaft along the rotation axis of the rotating body. The opening, said in a state of being penetrated by the rotational axis of the rotating body, according to claim 5 wherein the rotating member lower end or the rotating member lower end being connectable detachably by detachably connectable cap of the reaction vessel according to any one of Do stone claim 8. The rotating body is a nozzle capable of sucking and discharging a gas, the nozzle reactor according to claim 5 of stone claim 9 having its axis direction or rotational axis parallel to it. A storage chamber having an opening and capable of storing a liquid; a reaction chamber formed thinner or thinner than the storage chamber, at least a part of which is translucent or translucent; and A container having at least one flow path communicating with the reaction chamber, the container being formed so as to be connectable to a liquid introducing portion provided outside, and the reaction by connecting to the liquid introducing portion A reaction vessel capable of introducing a liquid into the chamber, wherein the storage chamber and the reaction chamber communicate with each other, and have a flow path that communicates the reaction chamber with the outside. It has a suction and discharge part that performs suction and discharge of gas through a nozzle, and the opening of the storage chamber can be connected by the nozzle,
The reaction chamber includes a pipette tip having a large-diameter portion and a narrow-diameter portion thinner than the large-diameter portion, and an outer surface of a core accommodated between the inner surface of the pipette tip and a spacer. It is a gap formed between the inner surface of the chip,
The storage chamber is a space in the large diameter portion formed above the reaction chamber,
The small diameter portion of the pipette tip is a flow path that communicates the outside and the reaction chamber,
The reaction vessel in which the opening of the large diameter portion can be connected by the nozzle. The reaction container according to claim 11, wherein various predetermined biological substances are arranged at predetermined positions on the outer surface of the core. Between the reaction chamber and the nozzle or the reservoir chamber, and wherein the said reaction chamber by clogging between the reaction chamber and the outside claims 11 was or can be sealed to claim 12 The reaction vessel as described. The reaction chamber is formed in a substantially cylindrical shape, the side surface of the reaction chamber, the height between the area is small and both the bottom surface than both bottom, stone claim of 1, which is thinner than the thickness of the reservoir chamber The reaction container according to claim 11 . One or more reaction vessels;
Having one or two or more liquid introduction portions to which the reaction vessel can be detachably connected;
The reaction container has an opening and a storage chamber capable of storing a liquid, a reaction chamber formed thinner or thinner than the storage chamber, at least a part of which is translucent or translucent, and the storage A container having at least one flow path communicating between the chamber or the outside and the reaction chamber, wherein the liquid is introduced into the reaction chamber by a liquid introduction unit, and the liquid introduction unit is a rotatable rotating body And a rotation drive unit that rotationally drives the rotating body, the rotation axis of the rotating body passes through the opening of the container, and the reaction chamber of the reaction vessel connected to the rotating body includes the storage The reaction vessel is formed so as to be located farther from the rotation axis of the rotating body than the chamber, and the reaction vessel is rotated by the rotation of the rotating body to introduce the liquid stored in the storage chamber into the reaction chamber. And
In addition, the liquid information measuring unit that obtains optical information in one or more of the reaction chambers, and a liquid introduction reaction measurement that causes the reaction of the liquid introduced into the reaction chamber by the liquid introduction unit and measures the optical information. apparatus. The liquid introduction reaction measurement according to claim 15, wherein the rotating body is a nozzle capable of sucking and discharging a gas, and a rotation axis of the nozzle is along or parallel to the axial direction of the nozzle. apparatus. The flow path of the reaction vessel has a liquid introduction flow path for introducing a liquid into the reaction chamber from the storage chamber or the outside, and an exhaust flow path for exhausting gas from the reaction chamber. And at least part or all of the flow path or the reaction chamber is formed of a deformable soft member,
The liquid introduction reaction measurement device according to claim 15 , further comprising a pressing portion that presses a predetermined portion of the soft member to seal the reaction chamber. One or more reaction vessels;
Having one or two or more liquid introduction portions to which the reaction vessel can be detachably connected;
The reaction container has an opening and a storage chamber capable of storing a liquid, a reaction chamber formed thinner or thinner than the storage chamber, at least a part of which is translucent or translucent, and the storage A container having at least one flow path communicating between the chamber or the outside and the reaction chamber, wherein the liquid is introduced into the reaction chamber by a liquid introduction unit,
In the reaction container, the storage chamber and the reaction chamber communicate with each other, and the reaction chamber has a flow path that communicates with the outside. The liquid introduction unit is configured to suck and discharge gas through the nozzle and the nozzle. The opening of the storage chamber can be connected to the lower end of the nozzle via a lower end of the nozzle or a cap connectable to the lower end of the nozzle,
The reaction chamber of the reaction vessel is a gap formed between an outer surface of a core housed in a pipette tip having a large diameter portion and a narrow diameter portion thinner than the large diameter portion and an inner surface of the pipette tip. Yes,
The storage chamber is a space in the large-diameter portion formed above the reaction chamber, and the small-diameter portion of the pipette tip is a channel that communicates the outside with the reaction chamber, and the large-diameter portion Can be connected by the nozzle,
A liquid introduction reaction measurement device that has one or two or more optical information measurement units that obtain optical information in the reaction chamber, and that causes the liquid introduced into the reaction chamber by the liquid introduction unit to measure the optical information. 19. The reaction container liquid introduction device according to claim 18 , further comprising a sealing means for fluidly closing between the nozzle or the storage chamber and the reaction chamber, and between the reaction chamber and the outside. Additionally, the liquid introduced into the reaction measuring apparatus according to claim 15 of stone claim 19 having a heating cooling unit which allows heating or cooling of the one or more of the reaction chamber. Wherein the reaction chamber of the reaction vessel, to further claims 15 having a sealing means for sealing the liquid-introducing reaction measuring apparatus according to any one claim of claim 20. The optical information measurement unit has one or more irradiation end portions for irradiating light to the reaction chamber, and one or more light receiving end portions for receiving light from the reaction chamber, and the irradiation end The portion is provided in contact with or close to the largest wall surface of at least one of the plurality of wall surfaces surrounding the reaction chamber, and the light receiving end portion is in contact with at least one of the wall surfaces excluding the largest wall surface or liquid introduction reaction measuring apparatus according to any one of the proximity to provided claim 15 of stone claim 21. The optical information measurement unit has one or more irradiation end portions for irradiating light to the reaction chamber, and one or more light receiving end portions for receiving light from the reaction chamber, and the irradiation end parts and receiving end, the liquid-introducing reaction measuring apparatus according to claim 15 of stone claim 22 provided in contact with the first wall surface of a plurality of wall or close surrounding the reaction chamber. The optical information measuring unit has one or more irradiation end portions for irradiating light to the reaction chamber, and one or more light receiving end portions for receiving light from the reaction chamber,
The heating / cooling unit has a heating / cooling end for heating or cooling provided in contact with or close to the reaction chamber, and the irradiation end of the optical information measurement unit and the heating / cooling end are 21. The liquid introduction reaction measuring device according to claim 20, wherein the liquid introduction reaction measuring device is provided in contact with or in proximity to one of a plurality of walls surrounding the reaction chamber. 25. The liquid introduction reaction measuring device according to claim 24, wherein the irradiation end portion is provided with a heating element or a cooling body of the heating and cooling unit. The heating and cooling unit has a heating end for heating that is provided in contact with or close to the reaction chamber, or a cooling end for cooling,
21. The liquid introduction reaction measuring device according to claim 20, wherein the heating end or the cooling end is provided in contact with or close to one wall surface having the largest area among the plurality of wall surfaces surrounding the reaction chamber. . The heating and cooling unit, a heating cooling end for heating or cooling, heat cooling end the pressurized, according to claim 20 provided relatively separable to the reaction vessel Liquid introduction reaction measuring device. The heating / cooling unit is provided with either a heating end portion for heating or a cooling end portion for cooling in each of the plurality of regions, and provides any one of a plurality of predetermined temperatures for each region. ,
21. The reaction chamber according to claim 20, wherein the reaction chamber connected to the liquid introduction portion and the heating end portion or the cooling end portion are relatively movable so as to approach or contact each other. Liquid introduction reaction measuring device. Gas for injecting gas at a temperature corresponding to the arrangement so as to cross the movement path direction at intervals between adjacent areas arranged along the movement path direction relative to the area of the reaction chamber The liquid introduction reaction measuring device according to claim 28, wherein an injection unit is provided. The optical information measuring unit has the light receiving end,
16. The reaction chamber connected to the liquid introduction section and the light receiving end are provided so as to be relatively movable so as to approach or contact each other and receive light from the reaction chamber. The liquid introduction reaction measuring device according to any of claims 29 . The optical information measuring unit has one or more irradiation end portion for emitting light to said reaction chamber, said irradiation end is separable therefrom a claim 15 provided to the reaction vessel The liquid introduction reaction measuring device according to claim 30 . The liquid introduction reaction measuring device according to claim 20, wherein the heating and cooling unit has a cooling end for cooling, and the cooling end is a blower for blowing air toward the reaction vessel. The reaction chamber of the reaction vessel is formed in a cylindrical shape, surrounded by two disk-shaped large walls and a small side wall, and receives one or more light receiving ends that receive light traveling in the radial direction of the cylinder The liquid introduction reaction measuring device according to claim 22, further comprising a portion. The optical information measurement unit includes two or more irradiation end portions provided at each irradiation position of the reaction chamber of the two or more reaction vessels, a plurality of types of light sources that respectively generate light having a plurality of types of wavelengths, One type of light from the light sources is selected by switching over time, and a light source selection unit that guides light to the irradiation ends at once, and each light reception of the reaction chambers of two or more reaction vessels Two or more light receiving end portions provided at a position, a light receiving position selecting portion for selecting light from each light receiving end portion by switching in time, and a plurality of types of opticals through which light from the selected light receiving positions should pass an optical filter selection unit for selecting a filter temporally switched, claim 15 of stone claims and a photoelectric device for sequentially inputting the light to a light passing through the optical filter selected from selected receiving position Item 34. The liquid introduction reaction measurement device according to any one of Items 33 . The optical information measurement unit includes two or more irradiation end portions provided at each irradiation position of the reaction chamber of the two or more reaction vessels, a plurality of types of light sources that respectively generate light having a plurality of types of wavelengths, A light source irradiation position selection unit that selects one type of light from the light source by switching over time and switches the selected light over time to guide each light receiving end, and two or more of the reactions Two or more light receiving end portions provided at each light receiving position of the reaction chamber of the container, and an optical filter selecting unit that selects and switches a plurality of types of optical filters through which light from the light receiving position should pass through liquid introduction reaction measuring apparatus according to claim 15 of stone claim 33 and a photoelectric device which sequentially enter the light that has passed through the optical filters. The optical information measuring unit has an irradiation end for irradiating light to the reaction chamber of the reaction vessel, and a light receiving end for receiving light from the reaction chamber, and the light receiving end with respect to the reaction chamber the light-receiving direction and an angular aperture at the incident and reflected path out determined based on the shape of the irradiation direction and the reaction chamber of the irradiation end portion, according to claim 15, wherein the receiving end is determined so as to receive light from said reaction chamber liquid introduction reaction measuring apparatus according to any one of Do stone claim 35.   1 or 2 or more rotating bodies that can rotate, 1 or 2 or more containers formed so as to be detachably connectable to the rotating body, and a rotation drive unit that rotationally drives the rotating body, the container Is connected to the storage chamber having an opening and capable of storing the liquid, and allows the liquid to pass therethrough. A working chamber provided to be shielded, and the working chamber is formed to be positioned farther from the rotational axis of the rotating body than the storage chamber, and the rotational axis of the rotating body is A liquid introduction apparatus that introduces liquid stored in the storage chamber into the working chamber through an opening. The liquid introduction device according to claim 37, wherein the rotating body is a rotatable nozzle capable of sucking and discharging gas, and the nozzle has a rotation axis along the axial direction thereof. 38. The liquid introduction apparatus according to claim 37 , wherein the medium is a filter having a predetermined pore diameter. The working chamber has a filter chamber having the filter in communication with the storage chamber, a storage chamber in communication with the filter chamber and detachably attached to the filter chamber, and by the rotation of the rotating body, 40. The liquid introduction apparatus according to claim 39 , wherein the liquid introduced into the filter chamber passes through the filter and reaches the storage chamber. The medium is a predetermined stationary phase, and the working chamber has a column in which the medium is stored and a storage chamber that is connected to the column and is detachably attached to the column. 38. The liquid introduction apparatus according to claim 37 , wherein the liquid introduced into the column by rotation can pass through the column and reach the storage chamber. The liquid introducing device according to claim 38, wherein the working chamber is formed thinner or narrower than the storage chamber. A step of accommodating the storage chamber of the reaction vessel according to the liquid to be processed to claim 1 of stone claim 14,
Introducing the liquid from the storage chamber into the reaction chamber of the reaction vessel;
Sealing the liquid in the reaction chamber by closing an opening or flow path provided in the reaction chamber;
Heating and cooling the liquid sealed in the reaction chamber;
A liquid introduction reaction measuring method comprising measuring optical information from the reaction chamber. The reaction container according to claim 11, wherein the opening has a cap that can be detachably connected to the opening. It said flow path and the reaction chamber, a flat frame having a groove or hole, is the frame according to claim 11 was or formed from a film of soft material covering the one side or from both sides of claim 44 The reaction container in any one.

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